Những xét nghiệm hóa sinh hiện đại sử dụng trong lâm sàng Phần 2

Tiếp nối phần 1 ebook phần 2 tiếp tục trình bày về các xét nghiệm: Xét nghiệm adrenomedullin, hs-CRP, Lp-PLA2, myeloperoxidase. Nhằm cập nhật các xét nghiệm hóa sinh, đồng thời phân tích ưu nhược điểm của từng xét nghiệm, nguyên tắc và phương pháp định lượng chúng,... Cuốn sách này sẽ giúp cho các nhà lâm sàng có thêm công cụ để chẩn đoán và điều trị bệnh lý nhiễm trùng và tim mạch.

ADRENOMEDULLIN Nguyjn Thi Bang Strang TONG QUAN YE ADRENOMEDULLIN Nam 1993, Kitamura va CS de phan lap mgt peptide mad tir u to bao ua crom (pheochromocytoma) cita ngugi va Tat ten la "adrenomedullin" (ADM) ADM kich,thich san xuet AMP yang (cycle AMP) tieu ceu gu6i va tac Ong rat manh, keo dai viec lam huyet ap ix chugt hixc nghiem Ban dau, ngugi ta nghi rang ADM chi dugc tong hgp bgi cac to bao u, nhien cac nghien,cdu sau d6 cho thy no ding dugc san thugng than va nhieu ca quan khac Ngay nay, ngtx6i ta uat b&i hang dinh tac dung dia ADM nhu 1a mot hormone luu hanh va chat trung gian can ti e/ t tai ch'6 vgi nhieu chirc nang sinh hoc quan 1.1 Ciu frac ciia ADM 52 Hinh 5.1 CSu trim phan tiv cua ADM 93 NHU'NG XET NGHIEM HOA SINH HIEN DAI SCP DUNG TRONG LAM SANG ADM dm nguai Om 52 acid amin Cau true cila no Mang dOng \Ted peptide lien quan den gen calcitonin (CGRP- calcitonin gene-related peptide), calcitonin va amylin, tat ca deu thtli)c ding gia dinh peptide Phan t* ADM chira mot \Tong Om acid amin dugc tao bai can not disulfua gifia acid amin so 16 va 21 (hinh 5.1), clau C tan ciaa ADM la acid amin tyrosin dugc lien k6t amid (-CONH-) Ca hai dee diem eau trtic rat can thiet cho hoat dOng sinh hoc dm ADM clang khong chira yang not phan t*, ADM clang gan vao receptor dm ADM nhimg khong có hoat tit-1h sinh hoc va no dugc sir dung nhu chat doi khong receptor dm ADM 1.2 Qua trinh sinh tong hcrp, bai tiet va chuyen h6a ADM dugc ma hoa bai gen nam tren nhi6m sac th6 so 11, gen chira exon va intron Dau tien chd6i DNA cUa ADM ma hoa tao phan tit den ADM preproADM, gem 185 acid amin Phan Ong phan cat doan peptide tin h* (Om 21 acid amin) tai vi trf gifra acid amin threonin (vi *1 21) va alanin (vi tri 22) se giai phong phan tit pro ADM Om 164 acid amin Pro ADM sau dugc enzym peptidase thily phan lam giai ph6ng ADM gom 52 acid amin va mot doan peptide khac a dau N ten Om 20 acid amin dugc goi 1a PAMP (Proadrenomedullin N-terminal 20 peptide) Ca hai phan tir ADM va PAMP &su có hoat tit-1h sinh hoc PAMP lam giam huyet dp truyen tinh mach chem, nhien tac dOng dm no yeu han so vai ADM Trong mot phan tich trinh tkr DNA cua preproADM nguai to phat hiO ADM dugc ma hoa bad exon thin va PAMP dugc ma h6a bai exon thin va thir Trong qua trinh phan cat preproADM, phan tit ADM -glycin- mot dang trung gian dia ADM (iADM: intermediate form) dugc tao Sau iADM dugc chuyen clang ADM throng (mADM) nho' enzym xtic tac tao lien ket amid, bai vey mADM có cau trite amid a dau C ten Dang *tieing cua PAMP dugc tong hop theo co che tuang tix nhu ADM (hinh 5.2) ADM có tiled gian ban hily ngan huye't (khoang 22 phut) va dugc dieu hoa bai enzym thily phan protein va nhiet luu trir nen có the anh hiking den ket qua Ngoai ra, mot vai yeu to khac c6 the lam ket qua xet ngh*n ADM khong chInh )(de lien ket vai protein lam irc the chuyen biet len ADM phucmg phap, thinnghi'01 mien dich phong xa Han the nika, hoat clOng tuang tac kieu ter tiet hoec can tiet 94 Adrenomodullin gift ADM va cac receptor dan den loaf bo peptide khoi clang Ulan hoan E2 E3 E4 EI AM locus Preproadrenomedullin Proadrenomedullin Thiry phan protein va amid hoa PAMP 1111111111-Glycin Imidation enzym Glyoin I oNn2 mADM PAMP 11111111111—coNH, Gian mach U'c ch6 giao cam Hinh 5.2 Sinh tong iADM Ha huy6t ap hov ADM, PAMP va tac dung sinh 19 cue chiing Mid-Regional proADM (MR-proADM) c6 47 acid amin, On, dinh rong tuan hoan han, duot tiet vai so Wang mol phan t* bang so mol illa ADM MR-proADM khong co hoax tinh sinh hoc nhu ADM, nen khOng bi anh huang bai enzym they phan protein Viec xac dinh nong dO VIR-proADM c6 the phan anh trgc tiep n,Ssng dO ADM mau benh nhan , Mix dO bieu hien mRNA dia ADM tang cao a thuang than va bieu hien thap han a tam nhi, tam that dia tim, than, phi va nhieu yang khac ciia nao Gen ADM ding bieu hien a to bao not mac mach mau va to bao ca Iran Qua trinh san xuat ADM dugc dieu Ma tang len bai cac ' tress oxy h6a, cac cytokine tin viem nhu TNF-a va IL-1, angiotensin II a endothelin-1 Anh huang dm stress len sr bai tiet ADM bad te, bac) not van dang gay tranh cai, Ca hai tac dung kich thich va iirc che deu da &rot mO ta Tinh trang thieu ,oxy kich thich giai ph6ng ADM a in vitro lan in vivo Tang &rang huyet gay tang bai tiet ADM mach mau thOng 95 NHU'NG XET NGHIEM HOA SINH HIEN DAI SO DUNG TRONG LAM SANG qua protein kinase C, lieu c6 the la met nhfing nguyen nhan lam tang ADM huyet tuong benh nhan dai than dueng Su truyen ANP (atrial natriuretic peptide) gay tang nong de ADM huyet tuong nguei Ca viec tang the tich mau cap va tang tai natri man Milt deu khong c6 bat ky anh huong nao den nong de ADM huyet tuong Aldosterone kich thich san xuat ADM or to bao co trop mach mau O My thugng than, ADM dugc &mg thei bai tiet vo7 catecholamine sau cac kich Mich bai tiet acetylcholine Ngugc lai vai cac peptide khac, ADM kh6ng dugc du trix cac hat tiet (ngoai trir a to bao not tiet cua tuy) ma dugc phong thich sau tong hop Neng de ADM huyet tuong dao deng khoang 2-10pM Ltic dau thugng than c6 the la nguei ta,nghi nong cao cila peptide nguen goc cua ADM huyet tuong, nhien nhieu bang chirng cho thay khong phal nhu vay Thir nhat, trai ngugc yeti catecholamine, nong de ADM tinh mach thugng than khong cao hon tinh mach chit duai Thin hai, cac kich Mich sinh 13'T dieu hea bai tiet catecholamine va ADM cna thugng than nhu dueng mau va huyet ap khong anh hueng den 'tong de ADM huyet tuong Mat khac nong de ADM huyet tuong khong tang Mei gian bi u to bao ua crom, catecholamine nhanh chong dugc giai phong Hien nguei ta tin rang ADM c6 nguen gOc chit' yeu tit cac to bao not me cac giueng mach mau khac nhau, T -)ng huyet tuong, ADM g&'n dac hieu vai protein-1 lien ket adrenomedullin ,binding protein-1), dugc xem thugr, than yeu to H lam tang tac dung qua nhu la yeu to th be the H Vic gan trung gian receptor cila ADM nhung lai tirc che hoat tinh khang khuan no Mat khac ADM lien ket se lam tang cueng dec lap vai receptor yeu to te H, la chat dc che dueng thay the hoat hoa be hoat deng the Sr tuong tac ADM-yeu to H coy nghia quan Tru6c het, ADM thuat xet lien k& vai ,protein khong dugc Oat hien bai hau het cac nghim huyet thanh, nhu vay nong de ADM toan phAn huyet c6 ie cao hon so vai se thuc,te dugc bao cao bad cac nghien ciru TruOrc day, nguei ta dal timg de xuat rang nong de ADM huyet tuong qua thap de tac deng tren cac receptor dm to &de va rang tac deng cita ADM chi tai cite eh* khong phai hormone luu hanh mau Quan niem hien da, bi thay d6i Ngoai ra, nong de ADM huyet tuong tang 96 Adrenomodullin cao met se benh canh lam sang, dee biet choang nhiem khuen huyet, có the la six thay doi dm peptide tix lien ket vei protein sang dang to vi giam 'long de cna bo the the H choang nhiem khuen Bei \Tidy, ADM toan phan choang nhiem khuen to huyet tren thuc te duoc danh gia rat cao cac nghien dru truec day Ngtroc lai vai ADM, ca CGPR (calcitonin gene-related peptide) va PAMP deu khong gen vei yeu to H ADM luu hanh mau bi phan giai nhanh chong voi thai gian ban huy khoang 20 pinit Neng de ADM huyet cieng mach chili thap lion deng mach phei, dieu goi y phi có the la not thai chinh cila ADM Nong de ADM nuec tieu cao gap 15 len so of huyet Wong ADM huyet tucmg de clang duvc loc qua tieu cau hen va sau bi phan giai bei cac endopeptidase trung hoe c6 ang to bao ria ban chai cue Ong 'Iron gan Mee du then co lien quan den su thai ADM nhung cac nha nghien ciru cho rang, peptide 1.rec tieu co nguon goc tix su san xuat tai cho then chic khong phai ix he thong tun hoan .3 Receptor va cac co' che" tru34n tin WO ADM hoat hoa va gen vei It nhet hai loai receptor lien ket protein G Met so tac dung dm ADM duot thuc hien qua trung gian cac receptor CGRP1 va bi ire the bei chat doi khang dee hieu vai CGRP1 la CGRP Cac receptor có di h„rc cao vei CGRP hen ADM Receptor ADM dee hieu bi de the bed ADM va co di luc vei ADM cao hen vei AGRP Nguoc lai, receptor CGRP khong gen vei ca ADM va CGRP Ong de pmol, ADM co kha nang,gan vei receptor caa calcitonin va dm amylin, nhien, khong chac chan cho rang la co che sinh 157 quan trong tac deng cua ADM Gen day, cau trtic phan to cue receptor ADM va receptor CGRP1 de duoc )(de dinh (bang 5.1) Ton tai hai loai receptor mang to bao, thuec gia Binh peptide calcitonin la receptor calcitonin (CTR: calcitonin receptor) va receptor giong vari receptor calcitonin (CRLR: calcitonin receptor-like receptor), cau true chinh dm chting tucmg &Ong vei den 55% Mei receptor ket hop vei met protein phu CO ten le RAMP (receptor activity-modifying protein) CO loai deng phan cna RAMP de 97 NHU'NG XET NGHIEM HOA SINH HIEN DAI SO' DUNG TRONG LAM SANG dugc xac dinh la RAMP1, RAMP2 va RAMP3 Cac protein RAMP ket hop \raj phan tir receptor Wed not sinh chat va tao dieu kin thuan lgi cho stx van chuyen chung mang sinh chat Ngoai ra, cac RAMP dieu,hea,mirc, d6 dm receptor glycosylation va có the la mot phan cna vi tri gin ket phi tir, quyet dinh tinh dac hieu cna receptor CRLR ket hop \Teri RAMP 1, hoac tao cac receptor tuong ang la CGRP1, ADM1 va ADM2 Tuang to nhu vay, CTR có the ket hop voi mot cac dang RAMP hinh ba clang receptor dm amylin la AM1, AM2 va AM3 (hinh 5.3) Ngoai ra, CTR khong lien ket RAMP hoat &Ong vbi to cach la receptor cna calcitonin Mac du cac (fang phan RAMP có s‘r khac biet viec phan bo a cac mo nhung khong co six khac biet ve dugc 15T gifra ADM1 va ADM2 hoac gifia ba loai receptor dm amylin Trong nhieu loai to bao, ADM va receptor CGRP1 ket hop vai protein, G va adenylate cyclase Ngoai ra, ADM co the lam tang hoac giam n6ng Ca' not bao d6c lap voi AMP veng ADM kich thich tong hop oxid nitric (NOS) to bao co tam that cna tho va t6 bao nOi mo ADM có the kich thich cac protein kinase hoat hoa phan bao (MAPKs: mitogen-activated protein kinases) to bao ca trop mach mau va irc che hoat dong cua MAPK a to bao trung mo Cuoi clung, ADM kich hoat kenh phu thu6c ATP to bao co trop mach mau d6c lap vai cac dueng tin hieu khac da dugc de cap a‘ teen Bang 5.1 CAu trim phan t:' dm receptor ADM va cac receptor lien quan Phan tiv receptor Protein RAMP C GRP, CRLR RAMP! CUR!' > ADM ADM, CRLR RAMP2 ADM > CGRP ADM2 CRLR RAMP3 ADM > CORP CFR CFR — AM, CFR RAMP! Amylin AM, CFR RAMP"_' Amylin AM, CTR RAMP3 Amylin Ten receptor 98 Kich thich Calcitonin Adrenomodullin Dan truy'en tin hieu cua ADM khac gifra the loaf to boo, lien chimg cho thy quan den mot so throng khac (hinh 3) viec kich hog hay gian doan tin hieu ADM di the gay nen the berth 1ST nhu thieu mau cue blo, gay ton thirang va pith trien khoi u Vi 4y, viec phat trien cac thuoc giup dieu hoa bai tiet ADM (long vai tro quan trong dieu tri chong tang sinh mach mau Cac th; 40.41:, oxy ve sytokanes, ffi He thOri re.retca ADACCSRP I ICGRP Reosplon RAMP ;Mt ReMOW: R/WP ;AtA2 Receptor RAMP LAMP Ct a, ligeNtri Phvc rcpt prom r bi, no■ rra P Te too„ PLC rakRet Mit() e126;AX•rAla Vat AC PCLC GCKrp r.AMPGW: coo MC s R"""2 • ' • AA wr.ft, PKG C, Diwir ate tnthrg Hint ttett Ong ixPofeets Ting iv atit try Sif Intimatbioi• Pea row,h Hinh 5.3 Tac dung &la ADM thong qua cac receptor Vai tr6 caa ADM qua trinh to kh6i u Vai tr6 caa thgu oxy va cac cytokine viem su' di6U h6a bgu Wan va bai tit ADM &xi cac to boo u ADM kich thich Sy' hinh kh6i u bang cach kich thich t6 boo u tang tru'&ng va ton tai th6ng qua cac y6u to can ti6t xung quanh mach mau HOAT TINH SINN HOC CUA ADM 2.1 Tic dung tren he tim mach ADM lam giam huye't op giam sirc can mach mau ngoai vi Di6su thugng di kern vod su tang cung lugng tim sau giam ha'u ganh Su giam slim can ngoai vi NIA huyet ap gay nhip nhanh phan x4, nhien, nhip tim tango mire thap hem so \Ted viec dung cac thuOc 99 NHU'NG XET NGHIEM HOA SINH HIEN DAI SU' DUNG TRONG LAM SANG dan mach lam 114 huyet dp Trong thgc nghiem, ADM lam dan mach cua cac gigerng mach mau khac va a cac loci demg vat khac Co che tac dung dan mach cua ADM da &roc de cap trong,nhieu nghien dm Cac dir lieu cho thay ADM c6 the gay dan not mo bang cach tac clOng vao cac receptor CGRP1 va lam tang AMP yang cac to bao co tron mach mau VI ADM duoc bai tiet bOi cac t6 bao not mo, no có the hog dOng nhu mot nhUng yeir to gay dan mach c6 nguOn goc not mo ADM cung có the kich hog cac kenh, kali to bao co tron lam tang six phan cgc cua to bao Ngoai ra, ADM gan voi receptor dac hieu a cac to bao not mo va gay dan mach not mo qua trung gian cua oxid nitric, yeu to phan cgc c6 nguOn goc not me (EDHF: endothelium-derived hyperpolarizing factor), va/hoac cac prostanoid dan mach ADM kich hog tong hop oxid nitric not mo (eNOS: endothelial nitric oxide synthase) beyi It nhat hai co che Thir nhat, ADM lam tang nong dO calci not bao, dieu lam tang hog Ong eNOS Thir hai, ADM hoat h6a enzym phosphatidylinositol 3kinase (PI3K) - va protein kinase B/Akt, gay phosphoryl hoa eNOS va tang hoat dOng cua no ca nOng dO Ca++ thap ADM cung c6 the irc che to bao not me, sari xuat yeu to co mach endothelin-1 ADM iirc che six den ch8 cua cac to bao co tron mach mau gay bai angiotensin II hoac yeu to tang trixOng co nguon goc tieu cau ADM c6 the dieu Ilea six tang sinh cua cac to bao co trop mach NO kich thich six tang sinh cac to bao co trop mach mot cach thu dOng ,ma kh6ng co six tham gia cac yeu to kich thich khac, nhung no che six fang sinh gay bad PDGF hoac huyet cua bao thai ADM irc che hien Wong chet to bao lap trinh cua to bao nOi mo gay bai sg thieu tuai mau Tac dung qua trung gian bai oxid nitric nhung khong phu thuOc vao GMP yang Mat khac, ADM kich thich tang sinh to bao not mo - qua trinh tham gia vao six tao mach va tai tao not mac cua mach mau bi ton thuang Anh htrang dm ADM tren chu kST to bao mach mau rat quan trong six tai tao ,mach mau tang huyet clOng mach hoac qua trinh phat trien tai hep sau phau thuat tai thong dOng mach Mac du viec truyen ADM lam tang cung luong tim nhung dieu khong quan bang giam six can ngoai vi Anh huang trirc tiep cua ADM tren six co bop co tim van gay tranh cai ADM lam giam co 100 Adrenomodullin bop t6 bao co tam that dm dig bang cach kich thich san xuat oxid nitric, gay giam Wong dg Ca++ a not bao thong qua co che phu thugc GMP yang Ngucec lai, ADM tac dung lam tang truong luc co dm tim chugt truyen don dgc va cilia co chugt Nhieu nghien cu u da chimg minh rang ADM che sinh tong tonghop protein va su phi,dai,co tim, cling nhu su tang sink nguyen bao soi tim va san xuat chat nen ngoai bao VI ADM ducec tong hop va bai tiet boi to bao co tim co 14p va nguyen bao sgi cua tim nen peptide c6 the dieu hoa su phi dai co tim va to chirc lai tang huyet ap gong mach hoac suy tim theo each can ti'etingi tiet Y nghia lam sang cua MR-proADM Gici tri tien (loan suy tim sau nhoi mau ca tim Nghien ciru mgt s6 luong lon bgnh nhan nhap vin vi nhgi mau co tim, nguai to da ket Juan rang nhitngo doi tucmg c6 Wong dg MR-proADM cao nhap thi c6 tS/ tien trien den suy tim cao hon Ngoai ra, loi Ich co ban stir dung MR-proADM co kha nang tien doan iduoc tir vong tren Nnh nhgi mau co tim (hinh 5.4) ,0 NI R- proADN1 < median - Ty le benh Olen song sot —4.4**unisormommaiwommowbowsw ‘,,41‘,Iwaigiminuriithst,vaimiumbhoinsee 0.8 NI R -pro A DN1 > median 0.4 - 0.2 - 0.0 0.00 00 00 20000 800 00 Ngay Hinh 5.4 Ty 10 suy tim ho0c ch0t theo MR-proADM 101 NHU'NG XET NGHIEM HOA SINH HIEN DAI SCY DUNG TRONG LAM SANG Gia tri ant MR-proADM ti'en Joan tir vong tren benh nhan kho tho cap Khi nghien ciru tren cac b6nh nhan nhap vien vi MI6 th6 cap Ngu6i ta nhan thay, nhfrng ngued c6 trieu chUng kho tha suy tim thi nong d6 MR-proADM (trung binh 1,6 nmol/L) cao hem so v6i nhang nguyen nhan khac (hinh 5.5) 5.0 4.0- C30- 1.0- 0.0 ADHF AECOPD Viern phOi Ranh ac tinh Tac Tang thong Barth khac phoi ph6i Chin clown Hinh 5.5 Gib tri MR-proADM chAn down nguyen nhan kh6 the, Ngoai ra, ngtx6i ta theo dOi ty 16 nhimg ngtr6i song sot khoang th6i gian nam va thay rang nong d6 MR-proADM tang cao (trung vi 1,9 nmol/L) dot tuong tit vong hon nhimg nguai 10 102 Myeloperoxidase LDL binh thuang (native LDL) ,kho c6 the gay it dong cholesterol to bao mach qua co che tir dieu hoa nhu giam cac thu the LDL va giai han su tong hop LDL qua enzym 3-hydroxy-3methylglutaryl coenzym A reductase Tuy nhien LDL bi bien d6i (modification), chd yeti la qua trinh oxy hoa, trey nen c6 vai tre chInh ca che hinh mang x0 vita, nhu it dong cholesterol qua su nhan biet bai cac thu the dm to bao don dep LDL it dung khoang duai not mach c6 the bi oxy hoa hay va se bi thuc bao bai cac dai thuc bao de hinh cac te to bao bot, dieu kien tien quy& de hinh mang xa Bang phucmg phap phan tich dinh lugng de xac dinh ve mat cau true phan tit cac marker cua qua trinh oxy hoa da xac dinh vai tre cua MPO va, cac san pham c6 di-1h oxy cua no viec chuyen LDL sang clang hien doi gay xa vita va vai phuang phap h6a m6 mien dich, khoi nguai to xac dinh vai tre MPO xtic tac tao cac chat oxy hoa dOng mach a benh nhan benh mach vanh: Chlorotyrosine, san pham dac trung cua su bien doi protein cac chat oxy hoa sinh tit six xtic tac cua MPO, co rat nhieu mo xa vita so vai mo a dOng mach binh thuang - Cac san phalli gay oxy h6a lipide bang cach ket hap chlor (co lien quan den MPO) ctimg hien dien rat nhieu mo xa vita so vai m6 ey dOng mach binh thuang - Cac san pham oxy hoa khac co the CO nguon goc tit six )(tic tac MPO nhu nitrotyrosine (clang co the hinh s cac nhom nitrogen tuang tac),.dityrosine ciing c6 nhieu xa vita LDL mau duac phan lap dr nhirng nguai bi xa vim co chira nhieu cac san pham ke tren so vai LDL a nguiyi kh6e manh MPO lam (hay dai chon loc Apolipoprotein A-I, lam raj loan chirc nang HDL Cac nghien cau gan day cho thay HDL la muc tieu cua su oxy hoa tit MPO mach va lam suy giam chirc nang cua lipoprotein HDL phan lap tir mang xa vt-ra co, mang nhieu peptide CO nguon gOc tir six oxy hoa có lien quan den kik tac caa MPO, bao gOm cac peptide bi bien &A phan -Cmg chlor hoa va nitrate hOa Ngoai HDL tuan hoan a nguai bi xa vita có gan vai MPO, dieu 151 NHCPNG XET NGHIEM HOA SINH HIEN DAI SO' DUNG TRONG LAM SANG phn hop \red cac phat hien,gan day la MPO g'an chon loc vOi apolipoprotein A-I huyet tuong tren vnng chu6i xoan (helix 8) cna lipoprotein Phan tich apo A-I thay rang or ngueri Nnh mach vanh ,phan nitrotyrosine (NO2Tyr) Ira chlorotyrosine (C1Tyr) c6 nong cao hon nguai kh6e manh Mix bien doi c6 lien quan den tan suat mac bOh dOng mach vanh,, mot nghien cite teen 100 doi tuong Nnh ngoai tru thay rang tuong c6 nong Apo A-I NO2Tyr va ClTyr a tam phan vi cao nhat c6 kha nang mac Nnh mach vanh cao,gap va 16 lan so vOi doi tuong tuong 'mg 6' tam phan vi thap nhat Nghien cuu pheng thfr nghisin va teen nguai deu cho thay cac HDL mang Apo A-I bi bien doi giam kha nang van chuyen ngugc cholesterol 1'6 rex so \Teri cac HDL c6 Apo A-I binh thuerng, no anh huang d6n,con duang luu cholesterol qua,ABCA-1 Ket qua in vitro thay rang HDL tip )(tic vOi HOC1 (chat oxy hoa MPO) canh tranh vOi eNOS cap diii eNOS Ming cap doi HDL binh thuong L-Arginine L-Arginine vi& gan vai scavenger • NADPH NADPH 02receptor BI, mot khau quyet dinh vi& hoi luu dm cholesterol Apo A-I phan lap tir mang xo vita c6 mixt bien doi nhi&I hon Apo A-I huy6t hay mo khac Dieu phn hop vOi cac bang L-Cltrulline L-Ci lline NO chnng hoa ma mien dich Superoxide ve viec oxy hoa Apo A-I xay sang thuong xo Hinh 8.3 Hai clang tac clo:ng cue eNOS vita nhieu hon d not khac MPO thric day gay rai loan chirc ruing not mach qua NO Nitric oxide (NO) duoc sinh xac tac cua enzym endothelial nitric oxide synthase (eNOS) la chat dan mach manh va qua no gift vai tro chInh dieu h6a truang luc mach mau Ngoai ra, NO ngan chan six ket dinh cua cac to bao tuan hohn vao not mo va nc che su 152 Myeloperoxidase tang sinh to bao co mach mau Noi chung, NO c6 vai tre then chot gift, an dinh not mai va thiL NO giam san xuat va/ho4c tang tieu thu deu gay suy chirc nang mach mau dan den xo vita MPO lam giam sinh kha dung (bio-availability) dm NO bang nhieu co ch6: NO c6 vai tre la co chat cua enzym peroxidase, MPO c6 th6 xuc tic lam giam NO Cac chat phan *rig c6 ngu6n gac xuc tic cua MPO sir dung NO la giam sinh kha dung oh NO Acid hypochlorous phan irng vai nguyen tit nito phan tit NOS gay tine ch6 tat ca d6ng clang NOS Acid hypochlorous la chat tao eNOS khong cap d'Oi (uncoupled eNOS), lam eNOS giam )(tic tic sinh NO (hinh 3) MPO va phat tri&I ming xe vfra doa vo , Mang xo vita mat on dinh va va tin trinh thi6t ye'tt clan s six co mach vanh cap MPO lam mat anh on dinh cua ming xa ,vita bang each hoat hoa enzym metalloproteinases, do lam yeu di nap xo cua ming xo vita Nhieu ket qua nghien citu cho thay ton thuang xo vita kich thich neutrophil giai ph6ng MPO, enzym lam mat on dinh ming xo vita va cac bang chimg h6a ma mien dich cho thay cac protein bi bien doi bai hypochloride va MPO c6 cling vi trf ma hoc cac mo xo vita Oai thgc bao cac vet ma khong china nhieu MPO, cac to bao sang thuang doa va lai china rat thieu MPO Tom lai MPO co lien quan den chuyen ming xo vita tix giai doan cu6i sang cac six co mach vanh cap THIEU MPO Nghien ciru thi6u MPO bat dau vao cu6i nhang nam 70, khoang thei ian nguai to chi mai phat hien 15 Nnh nhan 12 gia dinh bi thiL MPO Sau nh6 irng dung ky thuat deng to bao (flow cytometry) tren cac he thong tg dOng da phat hi6n them nhieu throng hop thieu MPO, tan suit kheang tren 1.000 — 2.000 dan Nhin chung bao cac 1:16i tugng van thgc bao binh thueng, nhtmg cham hoat tinh died khuan Khi6m khuy6t not bat nh'at la mat kha nang diet nam Candida cua 153 NHO'NG XET NGHIEM HOA SINH HIEN DAI SU' DUNG TRONG LAM SANG neutrophil, dieu phii hop vOi thuc to lam sang nguai ta thay rang có threw hop dugc thong bao nhiem khuan n4ng hay tai phat thieu MPO thi có den truang hop tir vong nhiem candida not tang, hoclan truang hop tir vong nam có den rOng MOt van de can luu throng hop bi dai thao duemg, ngued ta nghi nga có mot tinh trang khiem khuyet kep (double defect) thieu enzym MPO va benh dai did() &rang CAN THIEP DIEU TRI GIAM MPO M6i lien quan, gifia MPO va cac giai donbenh mach vanh da dugc xac dinh, dieu giiip xay dung chien lugc dieu tri giam hoat tinh )(tic tac cua MPO ke hoach phong ngira tier' phat va thir phat benh mach vanh Tra ngai lon nhat la nhang thuoc nhu vay se có tac dung lam suy chi:re nang cua cac enzym viec xuc tac bao ve co the vat chu Tuy nhien, chi nhang doi along bi thieu tram MPO moi tang nguy co nhiem khuan va MPO duoc,trir cac bach cau tuong dOi an toan khong bi tac dOng cua cac thuoc irc che vi no dirge trir nhan d dang tinh the, MPO chi dugc tiet vao cac phagolysosome va khoang ngoai bao dugc kich thich Mem soat enzym MPO la muc lieu cua dieu tri nham phong ngira benh tim mach Zhou va CS da cho thay atorvastatine lam giam MPO huyet va CRP benh nhan bi hOi chirng mach vanh cap XET NGHIEM MPO MPO có the hoat tinh mau va mo boi thir nghiem quang phO ke sir dung hydrogen peroxide va o-dianisidine dihydrochloride lam co chat Kh6J, luong MPO tunhohn dugc bang phuong phap ELISA Ngoai ra, MPO cfmg dupe neutrophil nhu la chi so huy nhan (degranulation) v6i may dem Coulter va phuong phap dong to bao (flow cytometry) Gan day, tren,thi truang dal co cac phuong phap cho phep hang lotgia thap Can tree lbn nhdt hien lam giam vai tro cua neng MPO irng dung lam sang (chi" yeu la phan tang nguy co benh mach vanh) la su khac ve 1c5% thuat phan tich: hai ky thuat phan tich enzym MPO thOng dung ten thi twang hien la khiWong (mass) va hoat 154 Myeloperoxidase tinh (activity), qua nghien dru cho hai kieu có tinh thong &Ong cao (r = 0,95), do khongthe the cho rang hoat tinh MPO thay vi khoi luting se anh huong den ket qua Thixc to cho thay chua có phuong phap nao (do hoat tinh hay kh6i Wang) tr6i hon thhc hanh can lam sang hien Tuy vay nhieu tac gia cho rang hoat tinh enzym dieu kien phong xet nghiem kh6ng thong &rig voi co the ngued (in vivo) Hoat tinh MPO chiu anh b6i nong dO cha d6ng co chat (co-subtrate) hydrogen peroxide, ma chat có nong dO kha cao khoang dui not mac (so voi mau), dac biet la nhang doi thong co nguy co cao lien quan stress oxy hoa flint but thu6c la, cao huyet ap, dai did° duong type 2, Trong phong this nghiem cac phan hng xay duOi six hien dien dm co chat va hydrogen peroxide & mirc bao hoa, hoat tinh enzym la chc dai nen có the pilaf' inh tot khoi Wang MPO (thong quan cao) M6t tr& ngai nfra la loci mau dung,‘ hien ngh&i ta thhemg dung huyet thong, huyet thanh, mau toan phan, to bao bach cau va mau mo Ngoai lay mau mau ngued ta con,tiem tinh mach heparin nham huy dOng MPO mau ngoai bien lam nong dO enzym cao hon binh thho'ng (baseline), dac biet la & benh nh'an benh mach vanh Heparin gay phong thich MPO tit bach cau va qua trinh dong mau kich hoat neutrophil, do loci 6ng, dung mau ding anh huong lon den ket qua Ong mau dong hay có chong heparin se lam tang 'long dO so voi 6ng chong &mg EDTA hay citrate Mau mau china 'Ong cO ,heparine có Binh neu gift lanh de & nhiet d6 nong d6 MPO thong d6i phong se lam tang nong d6 (có tai lieu cho rang nong dO MPO tang den lan chi gi6) Trong mau 'Ong có chong dong bang EDTA on dinh ca hai dieu kien, nhiet d6 pi-161).g va gift lanh Tin do, Shih va cac (fang nghiep khuyen cao clang 6ng nghiem co chong dong EDTA cho xet nghiem dinh 'hang MPO Tr& ngai khac viec d6i chieu, so sanh kat qua dinh Wong MPO la don vi phan lon la trinh bay clang phan tit (pmol/L) hay khoi luting (ng/ml), mot s6 It lai trinh bay clued clang tST so voi protein toan phan Chuyen d6i don vi ng/ml x 7.14 =pmol/L 155 NHU'NG XET NGHIEM HOA SINH HIEN DAI SO' DUNG TRONG LAM SANG 7.1 KS, tht4t phan tich Chucin bi matt - Mau me: Tong nhat mau mo (sau da loai be hoat tinh MPO mau) 50mM PBS (Phosphate Buffered Saline) MO dugc lam d6ng nhat de a -80°C de ly giai to bao Sau (long, ly tam mau > 10.000 vong/phat 30 phut g 4°C Phan chat long ben tren dugc dung - Mdu ly trich tir neutrophil (trong mau): loci be hong cau bang rang dextran Sau ly giai nhugc throng, lam tinh khiet bang cach dung ky thuat Ficoll Hypaque Hea loang neutrophil lai bang extraction buffer voi nong de 2x107 neutrophil/ml Sieu ly tam My phan dung dich not ben tren - Huy& hay huyet tuong: My mau tinh mach cho vao tube thich hop, tren deu, ly tam lay phdn dung dich phla teen (chti tuan thin yeu cdu cu the dm hang thuec, vi du tie lanh, ly tam lanh, chat cheng dong, ) ify dwelt dinh lurtg MPO mew - MPO - ELISA (dinh ltrong MPO) Nguyen tac: dtra tren nguyen tac cUa phan *ng hap phu bo the gan ket enzym phase ran (solid phase enzyme - linked immunosorbent assay) Ky thuat &mg met khang the don dong chong lai guy& dinh khang nguyen chuyen biet tren phan tir MPO Khang the khang MPO dugc &mg cho phase ran c6 dinh tren cac gieng phan *rig Khang the khang MPO khac gan voi horseradish peroxidase dugc cho vao va ket hop dang sandwich vOi ph*c hop khang nguyen-khang the cila phase ran, sau thei gian u cac khang the danh dau khong ket hop se dugc rua be TMB cho vao se phat trien mau xanh cita dung dich, them dung dich ngung phan *ng (stop solution) van lam mau dung dich chuyen sang yang va dam de tS, le vai nong de MPO mau 1(5T' thuat dugc nong MPO: 0,25 — 4Ong/ml a mau v6i tS, le 1/100, do ,khoang dugc nong mau ban au 25 -,4.000ng/ml Yong de vugt ngueng có the pha loang va tit* lai, ket qua nhan he so pha loang 156 Myeloperoxidase - MPO — activity (do hoot tinh MPO): Nguyen tac: Oa theo phan *ng cila Weiss va cac cl6ng nghiep mO to nam 1982 Duoi su mic tac MPO, acid hypochlorous (HOC1) dugc ,hinh (phan *ng 1) HOC1 nhanh chong phan dng vai taurine de' tao taurine chloramine Sau met thai gian * nhat dinh, phan Ilng \Tod su )(tic tac cila MPO dugc tam dimg bang cach cho vao catalase de loci b6 hydrogen peroxide Taurine chloramine sau se phan *ng v6i 5-thio 2nitrobenzoic acid (TNB), met ph*c hop co mau yang có de hap thu cuc dai tai bugc song 412nm Met don vi hoot di-1h enzym MPO dugc dinh nghia la luting enzym can thiet de xtic tac tao HOC1 du de hinh lnmol TauNHC1 pH = 6,5, nhiet de 25°C 30 phut, vgi su hien dien dm 100mM chloride va 1001.tM H202 De nhay phan tich: 10U/ml Tuyen tinh: 400 U/ml 7.2 frng dung 7.2.1 Phan tang nguy co' benh mach vanh et ngtrai khoe manh 1\16ng de MPO cang cao nguy co benh mach vanh cang cao, dec lap vai phan 16m cac yeu to nguy co truyen th6ng MPO co lien quan den hsCRP, so luting bach cau inau N6ng de MPO a nam cao hon nix, tang nhe theo tuoi va tinh tang but thuoc a nam va s* dung thuoc ngira thai O nguoi khee manh khong tien s* benh tim mach tuei tir 40 — 80 N6'ng de MPO huyet bang phuong phap ELISA met nghien dru benh chimg quy mo lon, Meuwese va CS thay rang: n6ng de nen oh nhom chUng (n = 2.237) co trung vi 638pmol/L (IQR: 454 — 951) thAp hon nhom benh (n= 1.138) 704pmol/L (492 — 1021) N'ong de MPO cang cao có nguy co mac benh mach vanh cang cao, &Si Wong ofi MPO > 951pmol/L (t* phan vi cao nhat) có nguy co mac benh tang oang 27% (sau dieu chinh vai cac yeu to nguy co truyen th6ng ,va s-CRP) so vai doi tuong c6 MPO < 454pmol/L (tir phan vi thap nhat) doi tuong có nguy co benh mach vanh thap (gam LDL-cholesterol < 305*1); HDL-.:cholesterol > 50mg/d1 va hs-CRP < 2mg/L), tang MPO ding Iam tang nguy co benh mach vanh va nguang thi uu ciaa MPO de phan tang nguy co a doi tuong la 728pmol/L 157 NHU'NG XET NGHIEM HOA SINH HIEN DAI SlY DUNG TRONG LAM SANG Cac nghien dm cat ngang ding nhan thAy neng de MPO d6i tuong hei chi ng mach vanh cap cao han nguoi kh6e manh, mirc de tang MPO c6 lien quan den de n'ang cua benh va six lan tea cua ton thuang xa vita DOng gop cua n6ng MPO thang diem nguy co Framingham nhieu tranh 7.2.2 Tien lung cae sce co mach vanh 6' benh nhan hOi cluing mach vanh cap N6ng de MPO c6 lien quan den Can suAt tai phat va tic vong cua hei chiing mach vanh cap Stephan Baldus va CS nghien ciau tren 1.090 benh nhan benh mach vanh cap nghien dm CAPTURE (c7E3AntiPlatelet Therapy in Unstable Refractory angina trial) nh4n thay nong de MPO huyet c6 trung vi 28711g/L (tir 1,5 den 1.112n/L) Tac gia nh4n thn'y diem c& gi6i han cna neng de MPO = 350mg/L (vi tri Bach phan 66th) gidp phan tang nguy co tir vong va nhoi mau d6i nghien cirus (ACS) Nhom benh nhan c6 MPO > 35011g/L c6 Can suAt tir vong va nhoi mau cao han c6 57ngliia so voi nh6m lai, khac biet gift hai nhom tang lien tuc den 72 gib sau khai phat Mat khac troponin T &roc xem la yen to den luting hei chung mach vanh cap vi c6 lien quan den mo ca tim hoai dr Nghien ctiru tren ding cho thay neng de MPO giup phan tang nguy co doi wow c6 TnT thAp '< 0,01R/L), doi argils c6 neng de MPO > 350n/L c6 tS le tit vong - a nhei mau tai phat la 15,9% sau thang theo doi so voi chi 2% cua doi Wong c6 MPO < 350µg/L N6ng de MPO a:mg gni') phan tang nguy co d6i Meng co hs-CRP trung binh (5 — 15mg/L) va thAp (< 5mg/L) Do neng de MPO cao gitip xac dinh cac doi tirong co nguy co cao tir nhang truarrig hop co hsCRP khong cao TAI LIEU THAM KHAO Stephan Baldus, Christopher Heeschen, Thomas Meinertz, Andreas M Zeiher, Jason P Eiserich, Thomas Mfmzel, Maarten L Simoons, Christian W Hamm Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes American heart association 2003; 108: 1440 — 1445 158 Myeloperoxidase Marijn C Meuwese, Erik S.G Stroes, Stanley L Hazen, Joram N van Miert, Jan Albert Kuivenhoven, Robert G Schaub, Nicholas J Wareham, Nicholas J Wareham, Kay-Tee Khaw, S Matthijs Boekholdt Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy Individuals Journal of the American College of Cardiology 2007; 50: 159-165 Joseph A Vita, Marie-Luise Brennan, Noyan Gokce, Shirley A Mann, Marlene Goormastic, Mehdi H Shishehbor, Marc S Penn, John F Keaney Jr, Stanley L Hazen Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans Journal of the American heart association 2004; 110: 1134-1139 Nauseef WM, Olsson I, Arnljots K Biosynthesis and processing of myeloperoxidase a marker for myeloid cell differentiation Eur J Haematol 1988; 40: 97-110 Roger K Schindhelm, Leonard P van der Zwan, Tom Teerlink and Peter G Scheffer Myeloperoxidase: A Useful Biomarker for Cardiovascular Disease Risk Stratification? Clinical chemistry 2009; 55(8):1462-1470 Valentina Loria, Ilaria Dato, Francesca Graziani, and Luigi M.Biasucci Myeloperoxidase: a new biomarker of inflammation in ischemic heart disease and acute coronary syndromes Hindawe publishing corporation 2008 Stephen J Nicholls, Stanley L Hazen Myeloperoxidase and Cardiovascular Disease Journal of the American heart association 2005; 25:1102-1111 Arnhold J Properties, functions, and secretion of human myeloperoxidase Biochemistry (Moscow) 2004; 69(1):8-15 Hoy A, Tregouet D, Leininger-Muller B, Poirier 0, Maurice M, Sass C, Siest G, Tiret L, Visvikis S Serum myeloperoxidase concentration in a healthy population: biological variations, familial resemblance and new genetic polymorphisms European Journal of human genetics 2001; 9:780-786 Tao Zhou, Sheng-hua Zhou, Shu-shan Qi, Xiang-qian Shen, Gao-feng Zeng,Hong-nian Zhou The effect of atorvastatin on serummyeloperoxidase and CRP levels in patients with acute coronary syndrome Clinica chemica acta 2006; 368(1): 168-172 159 BANG TRA Ttf 5-hydroxy-tryptophan, 26 6-pyruvoyltetrahydropterin, 26 7,8-dihydroneopterintriphosphate, 26 A Acid hypochlorous, 153 ADA, 43, 44, 45, 46, 47, 48, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 Adenosine, 43, 47 Adenosine deaminase, 43, 44, 57 ADM, 93-101, 104-113 Adrenomedullin, 86, 93, 96, 107, 108, 109 AIDS, 33 Alpha-TNF, 118 AMBP-1, 96 Angiotensin II, 72, 95, 100, 104, 105 ANP, 63-74, 77, 78, 83-85, 96 ANP-atrial natriuretic peptide, 63 Aanti-thymocyte globulin dan clang, 14 Apo A-I NO2Tyr, 152 apoA I, 149 ATI., 78 B Bach cAu dun nhan, 2, 7, 25-28, 38, 107, 108 Bach cau hat, Bai ti6t, 1, 3, 4, 6, 10, 25, 26, 30, 38, 50, 63-65, 67-73, 82, 94-96, 99-101, 104-107 Beo phi, 3, 79, 119 Biotin-SA-HRP, 109 BMI, 81, 137, 140 BNP, 63-67, 69, 70, 72, 79-87, 89, 103 Body mass index, 81 C CALC1, Calci, 1, 8, 100, 129 Calcitonin, Calcitonin gene-related peptide, 94, 97 CAP, 12, 13 Carcinoma, 2, CAT, 45 Catecholamine, 26, 70, 72, 96, 106 CGRP, 94, 97 Chan thirong, 6, 10, 13, 14, 15, 36, 108 Chat irc che thn the angiotensin, 82 Chemiluminescent assay, 122 Chloramin-T, 27 Chuye'n h6a, 2, 3, 8, 26, 43, 47, 48, 51, 54, 94, 137 ClTyr, 152 CNP, 63, 64, 65, 67, 69, 70, 72, 73, 85, 86 C-reactive protein, 115 Creatinin, 8, 30, 41 CRH, 105 CRLR, 97, 98 CRP, 4-6, 9, 11, 12, 16-21, 115-124, 126, 127, 139, 141, 154, 157, 158 CRP chuAn, 121 CRP-ph6i dr, 121 CTR, 97, 98 C-type natriuretic peptide, 63 Cycle AMP, 93 Cytokine, 4, 5, 7-11, 14, 31, 38, 95, 99, 107, 115 D Da day, 4, 31, 46, 65, 107 GAG, 4$ DMS-53, 160 Bang tra tip B Dai thao cluerng, 72, 79, 96, 126, 137, 141, 154, 155 Dai thixc bao, 25-28, 38, 45, 57, 63, 107, 116, 117, 130-132, 149-151 DiL flea, 9, 50 DO (lac hiO, 5, 6, 10, 16-19, 54-57, 74, 77, 78, 84 Do nhay, 5, 10, 15-18, 19, 36, 40, 50, 54-57, 74, 75, 77-79, 84, 115, 120122, 135 DOng hoc, 10, 12, 19, 20, 57, 58, 59, 78 Dung cong ROC, 21, 56, 76-78, 103 E Ecto - ADA, 43 Ecto-ADA, 52, 53 EDHF, 100 EDTA, 29, 87, 122, 134, 135, 155 ELISA, 29, 40, 41, 86, 88, 121, 132, 134, 135, 154, 156, 157 Endothelin 1, 85, 95, 100 Endotoxin, Eenzym, 1, 26, 28, 41, 43, 45-48, 5054, 57-59, 65-69, 72, 86, 87, 94, 95, 100, 104, 109, 121, 129, 130, 132, 133, 135, 140, 142, 147-149, 151157 Enzym phophatase, 26 Epstein-Barr virus, 32 Escherichia coli, extAdo, 52 GC, 47, 67 Gen, 3, 28, 45, 47, 49, 51, 66, 69, 94, 104, 107, 108, 130, 137 Gen HIV-1, 28 Ghep tang, 6, 15, 39, 40 Giarn mien dich, 15, 45, 51 Glucagon, Glucocorticoid, 9, 64 GMP yang, 65, 67, 68, 70-72, 100, 101 GTP, 26, 50, 68 GTP cyclohydrolase, 26 GvH (graft-versus-host), 40 HDL, 138, 149, 151, 152, 157 High sensitivity CRP, 121 HIV, 31, 32, 33, 34, 57 Hoi chUng Eissenmenger, 84 Hormone, 3, 4, 26, 48, 63, 73, 78, 79, 81, 93, 96, 105, 106 HPLC, 29, 30, 40, 41 HS-142-1, 72 hs-CRP, 115, 118, 120, 121, 122, 123, 124, 125, 126, 127, 138, 139, 140, 141, 157, 158 Hydrogen peroxide, 27, 58, 149, 150, 154, 155, 157 Hydroxyl hoa phenylalanine, 26 I iADM intermediate form, 94 IL-1 (3, IL-2, 9, 17, 52 IL-8, 17 Immunofluorescence, 121 Immunoturbidimetry assay, 122 in vitro, 7, 8, 25, 67, 95, 152 INH-y, iNOS, 8, 28 Interferon-?, 25, 26, 27, 28, 31 Interleukin 1, 3, 118 Interleukin 6, 3, 118 IP3, 48 F Fluorescent tracer, 121 Folate, 27 G Gan, 2-4, 7, 8, 26, 32, 39, 40, 46, 51, 57, 58, 72, 115, 118, 119 Gastrin, 161 NHU'NG XET NGHIEM HOA SINH HIEN DAI SO' DUNG TRONG LAM SANG K Katacalcin, 1, Khang sinh, 5, 15, 19, 20, 27 Khang the, 7, 8, 32, 33, 41, 53, 87, 105, 107, 109-111, 117, 120, 121, 135, 136, 148, 156 Kh6 th6, 75, 79, 86, 102 Kich thich, 1, 3, 7, 9, 13, 14, 25, 26, 28, 29, 31, 43, 45, 48, 49, 52-54, 64, 6873, 82, 93, 95, 96, 98-101, 104-108, 113, 123, 148, 149, 153, 154 Kryptor, 15, 16 Ky sinh trimg, 21, 31, 34, 117 L Latex turbidimetry, 121 LDL, 28, 126, 127, 130, 131, 138, 139, 149, 150, 151, 157 LDL-cholesterol, 126, 127, 138, 157 L-dopa, 26 Lepidoptera, 25 Lipopolysaccharide, 7, 117 Lp-PLA2, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142 LUMItest, 15 Lupus, 37 Lympho B, 7, 46, 51 Lympho T, 31, 46, 47, 53, 54, 118, 130, 131 Lymphokin, 25 Lyso-PC, 131 M mADM, 94 MAPK, 98, 106 Melanoma, 14 MiJn dich, 3, 6, 15, 16, 25, 26, 29, 31, 37-39, 41, 43, 46, 51, 53, 54, 86, 94, 106, 109, 117, 121, 122, 132, 133, 135-137, 151-153 MiL dich phat quang, 15 MO m&, 3, MPO, 147-158 MPO-H202-halide, 148 mRNA, 7, 47, 52, 95 MR-proADM, 77, 78, 95, 101-103 MR-proANP, 74-79 Mirc loc ciu thin, 71, 72, 80, 81 Myeloperoxidase, 147 N NaC1 sinh 1Y, 29 Naked DNA, 117 Nim candida, 14 Natriuretic peptide, 63 Neopterin, 25, 27, 28, 29, 31, 33, 36, 40 Neuroborreliosis lyme, 36 NhiJm khan, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 31, 36, 46, 57, 88, 97, 119, 120, 121, 154 Nhi6m khan huy6t, 2, 17, 18, 19, 20, 21, 36, 97 NhiJm sac th& 3, 51, 67, 94, 118, 130, 147 NhOi mau co tim, 14, 38, 69, 77, 78, 101, 115, 123, 126, 127, 140, 141 NO, 28, 149, 150, 152, 153 NO2Tyr, 152 NOi clOc to, 5, 7; 8, 9, 31, 107 NOS, 49, 98, 153 NPPC, 67 NPR-A, 67, 68, 73 NPR-B, 67, 68, 73 NPR-C, 67, 68, 69, 73 NT- proANP, 74 NT-proBNP, 67, 79, 80, 81, 82, 83, 86, 103 NT-proCNP, 85, 86 162 Bang tra tiv • KT3, Oxy hoa khir, 28 P PAF, 129, 130, 131 PAMP, 94, 95, 97 PCT, 1-22 PDA, 84, 85 PDGF, 100 Peptide, 2, 3, 63-70, 72, 73, 93-97, 101, 104-106, 109, 147, 148, 151 Peroxyl lipide, 28 PGE2, 50 pH, 8, 27, 29, 40, 45, 58, 157 pH man, Pha dao ngirac, 29 Phan ang chuye'n methyl dia t6 bao, 51 Phat x4, 29, 112, 113 PhAti thuat tim, 7, 10, 12, 85 Phien ma, 27 Ph6i, 2, 3, 4, 6, 14, 17-19, 34, 35, 46, 51, 54-57, 64, 84, 85, 95, 97, 108, 115 Phosphate Sorensen, 29 Phosphocholine, 117 PI3K, 100 PIP3, 50 PKB, 50 Plasmodium falciparum, 14, 34 PLC, 48 PMPs, 129 PreproADM, 94 Preprocalcitonin, Proadrenomedullin N-terminal, 94 Pro-ANP, 66, 67, 69, 73 Pro-BNP, 67, 69, 79 Procalcitonin, Protein, 1, 2, 3, 9, 41, 45, 48-50, 53, 56, 57, 68, 69, 78, 94-98, 100, 101, 115, 129, 147, 148, 150, 151, 153, 155 Proteomic, 83 Proto-oncogene, 28 R RAMP, 97, 98 Receptor CGRP1, 97, 98, 100, 104, 105 Renin-angiotensin-aldosterone, 70 RIA, 40, 41 RL95.2, 107 ROC, 77 S SA-HRP, 109, 110, 112 SCID, 51 Serotonin, 26 Somatotatin, S6t ret, 12, 14, 21, 34 Sot xuat huy6t Dengue, 21, 33 Standard CRP, 121 Suy da ca quan, 6, 15, 19, 36 Suy than, 40, 64, 79 Suy tim, 37, 63, 64, 69, 72, 74-83, 85, 86, 101, 102 T Tam soat, 75, 76, 79, 120 Tam thu, 77, 80, 83, 84, 86 T6 bao C, 1, 3, 5, 33, 53 Thai ghep, 14, 31, 39, 40, 69 Than kinh not ti6t, 3, 7, 26, 77 TIA, 133, 134, 135 TNF-a, 2, 3, 8, 9, 14, 17, 26 TNF-a va IL-1, 95 Traditional CRP, 121 Tre so sinh, 14 Tuan hoan, 4, 6-9, 14, 63, 67, 69, 73, 74, 81, 84-86, 95, 97, 104, 129, 131, 151, 152, 154 Tuy6n giap, 1, 2, 3, 5, 6, 9, 14, 49 Tyrosine, 26, 150 163 NFILYNG XET NGHIEM HOA SINH HIEN DAI SO' DUNG TRONG LAM SANG Virus, 5, 10, 14, 15, 21, 22, 25, 31, 32, 33, 35, 40, 46, 57, 119, 148 Vitamin D, VSMC, 108 U tic the men chuye'n (ACEi), 82 Ung thu to bdo nho, Ung thu thAn kinh, V Vi khudn, 3, 5, 9-11, 15, 27, 31, 34, 35, 45, 106, 107, 115, 117, 119, 148 Vi khudn Gram am, 31 Viem cap, 15, 119 Viem mang ndo, 16, 18, 21, 22, 36, 46, 55, 56 Viem mang nao mu, 18, 21, 22, 46, 56 X X-quang, 76, 79 z ZG, 105, 106 a-MSH, 26 Chiu trach nhiem xult ban: HOANG TRQNG QUANG TRAN THUY HONG Bien Op va Sua ban in: TRAN THUY HONG In 1.000 cuon kh6 16x23,5cm tai TNHH SX-TM-DV-IN THAI DUONG, Quach HOu Nghiem, Q Tan PhO, TP HCM S6 clang ky ka hoach >mat ban: 23-2013/CXB/322-185NH S6 xuat ban: 75/QD-YH 05/3/2013 In xong va nOp Iglu chidu quY 11/2013 164 CONG CHI NHP Dia chi: 699 DiOn thoai: Email: nxoynoc_cn *F-2013-0001* 61 L Gia : 150.000d ... Rev Cytol 20 02; 22 1:1- 92 Review Martinez A, Miller MJ, Catt KJ, Cuttitta F Adrenomedullin receptor expression in human lung and in pulmonary tumors J Histochem Cytochem 1997 Feb; 45 (2) :159-64... patients with acute chest pain Heart 20 12 Dec Zudaire E, Portal-NUriez S, Cuttitta F The central role of adrenomedullin in 12 host defense J Leukoc Biol 20 06 Aug;80 (2) : 23 7-44 114 hs-CRP Trim Thanh Vinh... TRONG LAM SANG SINH TONG HOT Gen tong hop CRP 11'am tren nhie'm sac the thin (1q21-q23), Om exon rieng biet va intron, mot exon ma Ma acid amin d'au va mot exon ma boa 20 4 acid amin lai CRP sinh