Trypsin, Chymotrypsin và Elastcug"n "gpfqrgrvkfcug."e„"pij c"ej¿pi"e逸v"ejw厩k" rtqvgkp"v衣k"eƒe"p嘘k"rgrvkfg"d‒p"vtqpi"o衣ej"pj逢pi"o厩k"gp¦{og"u胤"vj栄{"rj¤p"逢c"vj ej" eƒe"p嘘k"m隠"e壱p"x噂k"mk吋w"i嘘e"czkv"cokp"8員e"vt逢pi0"Vt{rukp"e逸v"p嘘k"rgrvkfgpic{"v衣k"eƒe"
nhóm ectdqp{n"e栄c"i嘘e"czkv"cokp"mk隠o*n{ukpg"jc{"ctikpkpg+0""Ej{oqvt{rukp"e逸v"pic{" e衣pj"i嘘e"czkv"cokp"vj挨o"*rjgp{ncokpg."v{tqukpg"jc{"vt{rvqrjcp+0"Gncuvcug" v"rj¤p" dk羽v"j挨p"pj逢pi"逢c"vj ej"eƒe"i嘘e"czkv"cokp"pj臼"m液"p逢噂e"pj逢"cncpkpg0
Trypsin: Rn =Lysine (K), Arginine (R)
14
Hình 2.8: Vt{rukp."ej{oqvt{rukp"x "gncuvcug"*vjw瓜e"nq衣k"Ugtkpg"Rtqvgcug+
Ba enzyme này x¿e"vƒe"vjw益"rj¤p"rtqvgkp"v衣k"eƒe"p嘘k"rgrvkfg"d‒p"vtqpi"x噂k"eƒe"mk吋w" czkv"cokp"mjƒe"pjcw0"Vt{rukp"逢c"vj ej"eƒe"i嘘e"n{ukpg"jc{"ctikpkpg="ej{oqvt{rukp"逢c" vj ej"eƒe"czkv"cokp"ejw厩kd‒p"x”pi"vj挨o"x "gncuvcug"逢c"vj ej"eƒe"i嘘e"czkv"cokp"pj臼"
không e詠c.
2.3. Eƒe"nq衣k"Rtqvgcug
2.3.1. Endopeptidase và Exopeptidase
Gp¦{og"8逢嬰e"rj¤p"e逸v"d荏k"e挨"ej医v"rtqvgkp"v衣k"nk‒p"m院v"cokfg"8逢嬰e"rj¤p"nq衣k"n " rtqvgcug"jq員e"rgrvkfcug0"J亥w"j院v"eƒe"rgrvkfcug 8逢嬰e"dk院v"8院p"vjw瓜e"o瓜v"vtqpi"jck" pj„o"ucw."rj映"vjw瓜e"x q"x鵜"vt "8員e"jk羽w"v衣k"nk‒p"m院v"rgrvkfg"e栄ce挨"ej医v0
‚ Endopeptidase:
P院w" nk‒p" m院v" rgrvkfg" d鵜" 8泳v" v衣k" x鵜" vt " nk‒p" m院v" d‒p" vtqpi" o衣ej" e栄c" o瓜v"
pol{rgrvkfg"vj·"gp¦{og"p {"i丑k"n "gndopeptidasẹ Trong nhóm này có chymotrypsin
x "vt{rukp0"Eƒe"vk隠p"ej医v"e栄c"eƒe"gp¦{og"i丑k"là eƒe"¦{oqigp."pij c"n "ej医v"u違p"ukpj" tc"gp¦{og0"Eƒe"¦{oqigp"e„"vt丑pi"n逢嬰pi"rj¤p"v穎"j挨k"ecq"j挨p"gp¦{og"x·"e„"ocpi" vj‒o"o瓜v"8q衣p"rgrvkfg0"E逸v"rgrvkfg"p {"i丑k"n "jq衣v"j„c"¦{oqigp"8吋"ukpj"tc"gp¦{og"
O A sp O O N H A la O N H Lys N H3+ O E la s t a s e T ry p s in N H O N H P he O C h y m o try p s in N H H O S er O E la s t a s e N H O N H Leu
15
8吋"n o"zw医v"jk羽p"jq衣v"v pj0"Vtqpi"e挨"vj吋."vtqpi"v院"d q."eƒe"gp¦{og"jk羽p"fk羽p"荏"f衣pi" ¦{oqigp"x "ej雨"8逢嬰e"jq衣v"j„c"8吋"jq衣v"8瓜pi"n¿e"e亥p"vjk院v0
Vt{rukp"e逸v"p嘘k"rgrvkfg"pic{"v衣k"eƒe"pj„o"ectdqp{n"e栄c"i嘘e"czkv"cokp"dcse (lysine hay arginine). Chymotrypukp" e逸v" pic{" e衣pj" i嘘e" czkv" cokp" vj挨o"
(phenylalanine, tyrosine hay tryptophan).
Rj違p"泳pi"vj栄{"rj¤p"gpfqrgrvkfcug
‚ Exopeptidase:
P院w"nk‒p"m院v"rgrvkfg"8泳v"v衣k"ew嘘k"cokpq"jq員e"ew嘘k"ectdqz{n"e栄c"o瓜v"e挨"ej医t
rtqvgkp."gp¦{og"8„"i丑k"n "gzqrgrvkfcug0"F詠c"x q"x鵜"vt "8泳v"ew嘘k."o瓜v"gpfqrgrvkfcug" e„"vj吋"n "cokpqrgrvkfcug"jq員e"ectdqz{rgrvkfcug.
16 2.2.2. Enzym jq衣v"8瓜pi"8員e"jk羽w<
E挨 ej院"rj違p"泳pi"fq"eƒe"Rtqvgcugz¿e"vƒe"8逢嬰e"ejkc"vj pjp<o"nq衣k"[22] + Serine Protease
+ Cysteine Protease
+ Aminopeptidase (metallo-exopeptidase) + Carboxypeptidase (metallo-exopeptidase) + Acid Protease
DＶpi"2.4: T pj"8員e"jk羽w"x "ej泳e"p<pi"Rtqvgcug [35]
Nq衣k"Gp¦{o Zƒe"8鵜pj"jq衣v"v pj Enzyme cЦ thЕ thШТng gωp Ej泳e"p<pi" Ej医v"泳e"ej院 Protease Ej泳e"p<pi
Serine protease ÐCevkxgÑ"
serine Fluorophosphates Trypsin Tiêu hóa (Digestion)
Thrombin A»pi"oƒw
( Blood coagulalation )
Plasmin Vk‒w"e映e"oƒw"8»pi
(Lysis of blood clots)
Conoonase E挨"j丑e (Mechanical)
Subtilisin Tiêu hóa
Acrosin Z¤o"pj壱r"e栄c"vkpj"vt́pi
(Sperm penetration) Metallo-
exopeptidase
Zn2+ EDTA, EGTA Carboxypeptidase Tiêu hóa
Sulfhydryl CySH o-Phenanthroline Papain Tiêu hóa
Idoacetate Streptococcal Tiêu hóa
Protease P瓜k"d q (Intracellular)
Cathepsin B Tiêu hóa
Acid Protease Acidic pH
optimum
o-Phenanthroline Thermolysin Tiêu hóa
Pepsin Tiêu hóa
17
Các serine protease jq衣v"8瓜pi"swc"pjóm ÎQJ"e栄c"Ugtkpg0"A吋"dk院v"o瓜v"rrotease là serine rtqvgcug."e„"vj吋"f́pi"rj逢挨pi"rjƒr"d医v"jq衣v"8員e"jk羽w<"ugtkpg"rtqvgcug"d鵜"jq p" vq p"d医v"jq衣v"pjcpj"d荏k"fkisopropyl fluorophosphates (DFP+"fq"ej医v"p {"i逸p"8欝pi"vt鵜" x q"vtwpi"v¤o"jq衣v"8瓜pi"ugtkpg"swc"nk‒p"m院v"rjqurjcvg"guter [23].
2.4. ChЭc n¾ng sinh hНc:
Các protease 8„pi"pjk隠w"xck"vt”"ukpj"j丑c vtqpi"v院"d q"x "e挨"vj吋0"
DＶpi"2.5: O瓜v"u嘘"ej泳e"p<pi"ukpj"j丑e"e亥p"8院p"xck"vt”"e栄c"Protease [4] Ch泳c n<ng ukpj"j丑e1 sinh lý Ch泳c n<ng enzyme c映 th吋 E挨"ej院"d違q"x羽"*Fghgpug"ogejcpkuoư
U違p"zw医v"Jqtoqp"(Hormone production)
A挨p"x鵜"8衣k"rj¤p"v穎"*Ocetqoqngewnct"
assembly)
Tiêu hóa (Digestion)
Rjƒv"vtk吋p"*Fgxgnqrogpv+
A»pi"v映"oƒw ( Blood coagulation) Ti隠n Insulinå Insulin
V衣q FibrinåFibrin
V衣q CollagenåCollagen Zymogen åJq衣v"j„c protease
Prococoonaseå Cocoonase
V鰻pi"j嬰r"Prochitn åV鰻pi"j嬰r"
Chitin
O瓜v"u嘘"ej泳e"p<pi"x壱v"n#"pj逢<"e挨"ej院"d違q"x羽"e挨"vj吋"mjk"d鵜"v鰻p"vj逢挨pi"vj·"dk吋w" jk羽p"d茨pi"e噂"ej院"8»pi"v映"oƒw."n o"n pj"x院v"vj逢挨pi0"Piq k"tc"ej¿pi"e”p"e„"ej泳e"p<pi" vk‒w"j„c"n o"dk院p"8鰻k"eƒe"vk隠p"ej医v"¦{oqigp"jq衣v"j„c"vj pj"eƒe"rtqvgcug"jq衣v"8瓜pi0"
Các ch泳e"p<pi"vt‒p"8逢嬰e"8k隠w"vk院vswc"jq衣v"8瓜pi"e栄c"eƒe"rtqvgcug.
X噂k"eƒe"8員e"v pj"x "ej泳e"p<pi"ukpj"j丑e"p‒w"vt‒p."vc"e pi"vj医{"t茨pi"ugtkpg" rtqvgcug"e„"vtqpi"p丑e"t逸p"n映e"e pi"ej pj"n "eƒe"vk隠p"ej医v"¦{oqigp"8逢嬰e"jq衣v"jqƒ" vj pj"eƒe"rtqvgkp"jq衣v"8瓜pi"mjkp„"x q"vtqpi"e挨"vj吋"d鵜"pjk宇o"p丑et逸p"n映c.
2.2.2. Protease trong n丑c r逸n l映c
P丑e"t逸p"n "o瓜v"rj泳e"j嬰r"i欝opjk隠w"gp¦{og, protein, pj英pi"rqn{rgvkfge„"8瓜e" v pj."x "eƒe"vj pj"rj亥p"x»"e挨. Các enzyme 8«"zƒe"8鵜pj"n phospholipase A2,L-amino acid oxidases, metalloprotease và serine protease [38]0"Vj pj"rj亥n protein và peptide
18 P丑e"t逸p #ﾏｷﾐｷﾗ"#IｷS " 迂"Sﾗ 1=I"Nﾗﾐ"[ｷﾏ"ﾉﾗ緯ｷ Amines Nucleosides Lipids Carbonhydrates Proteins và Peptides (90-95%) Enzymes
Metallo- và Serine proteases
Phosphomonoesterases Proteins và Peptides 9引I" 咽"1yN}v Cystain NGF và VEGF ]WI ｷﾐ"S緯ﾐｪ"1 9引I" 咽"H;"ﾐｪﾙﾐ" ; Peptides Myotoxins 1ｴ萎 "右I"Iｴ壱"v ﾗ W; W Enzymes Enzymes Phosphodiesterases Paraoxonases
HEP Arinaselike enzymes Hyaluronidases Acetylcholinesterases NAD Nucleosidases Endonucleases Arylamidases PLA2S LAAOS Hình 2.9: Eƒe"vj pj"rj亥p"e栄c"p丑e"t逸p Vj pj"rj亥p"e栄c"p丑e"t逸p"rj映"vjw瓜e"x q"pjk隠w"{院w"v嘘"pj逢"fk"vtw{隠p."vw鰻k."ik噂k"v pj." vj泳e"<p."e逢"vt¿"e栄c"v瑛pi"nq k"f磯p"8院p"違pj"j逢荏pi"8院p"j厩p"j嬰r"v詠"pjk‒p"e„"vj吋"i¤{"d医v" 8瓜pị"i¤{"ej院v"x "vk‒w"j„c"eqp"o欝k"[14].
19
P丑e"t逸p8瓜eej泳c"pjk隠w"rtqvgkp"e„"vƒe"8瓜pi"x q"j羽"e亥o"oƒw."o瓜v"u嘘"v逢挨pi"vƒe" x噂k"eƒe"{院w"v嘘jq員e"vƒe"8瓜pi"vt‒p"vk吋w"e亥w"x "eƒe"vj pj"rj亥p"mjƒe"e栄c"j羽"vj嘘pi"e亥o" oƒw0" O瓜v" u嘘" protein là các enzyme pj逢" pwengqvkfcug, phospholipase A2, metalloprotease và serine protease, trong khi lectin f衣pi"E và disintegrins, cjq"vj医{" mj»pi"e„"jq衣v"8瓜pi"gp¦{og0
Vtqpi"8隠"v k"p {.mj違q"uƒv"ugtkpg"rrotease và 3 enzyme 8員e"vt逢pi"rj鰻"dk院p"n : trypsin, chymotrypsin và elastasẹ
Ac"u嘘 gp¦{og"vjco"ikc"vtqpi"xk羽e"8»pi"oƒw"e pi"n "eƒe"ugtkpg"rtqvgcug."eƒe" gp¦{og"p {"vw亥p"jq p"vtqpi"oƒw"荏"f衣pi"vk隠p"gp¦{og"*zymogen) ej逢c"jq衣v"8瓜pi"x " ej雨"8逢嬰e"jq衣v"j„c"mjk"o衣ej"oƒw"d鵜"v鰻p"vj逢挨pị"jq衣v"jqƒ"n o"¦{oqigp"o医v"o瓜v"8q衣p" rgrvkfg."v泳e"e pi"fq"o瓜v"rtqvgkp"e逸v<"vt{rukp"jq衣v"j„c"vt{rukpqigp"p‒p"jq衣v"jqƒ"n " o瓜t c挨"ej院"pjcpj [7]0"P欝pi"8瓜"e挨"ej医v"違pj"j逢荏pi"n噂p"8院p"x壱p"v嘘e"rj違p"泳pi"fq"
enzyme xúc tác.
Vtqpi"e挨"vj吋"pjk隠w"Gp¦{og"épi"jq衣v"8瓜pi"x "rj嘘k"j嬰r"8k隠w"vk院v0"A嘘k"x噂k"o瓜v"
enzyme:
+ V嘘e"8瓜"rj違p"泳pi"z¿e"vƒe"n羽"vjw瓜e"x q"p欝pi"8瓜"e栄c"gp¦{og"]G̲x "e栄c"e挨"ej医v" ]U̲0"E„"gp¦{og"v嘘e"8瓜"n羽"vjw瓜e"x q"jck"e挨"ej医v"*eƒe"qxydo - tgfwevcugư0"V嘘e" 8瓜"e”p"n羽"vjw瓜e"x q"o瓜v"u嘘"{院w"v嘘"mjƒe0 雲"o瓜v"p欝pi"8瓜"]G̲"?"Evg"x "]U̲"?Evg"vj·< P t (giây) g v嘘e"8瓜" DCP"A井W + èk"n詠e"G"x噂k"U V嘘e"8瓜"zqc{"x亥p"z¿e"vƒe"*vwtpqxgt"tcvg+
20 k1 Ikck"8q衣p"z¿e"vƒe k2= kcat k2 k-1 + 雲"ikck"8q衣p"vtwpi"ikcp"p欝pi"8瓜"e栄c"rj泳e"j嬰r"]GU̲"n "ik噂k"j衣p"e栄c"v嘘e"8瓜"rj違p" 泳pi 計暢 噺喧月µ券"健検"継鯨 建徊剣"継鯨 噺 " 倦貸怠髪"倦態 倦怠
+ Khi [S] >>[E] å[ES] [ET] ( [ET]=[E] + [ES])
Fq"8„"v å VMAX =kcat [ET]
I丑k"G"n "gp¦{og."U"n "e挨"ej医v."GU"n "rj泳e"ej医v"vtwpi"ikcp."R"n "u違p"rj育o"ew嘘k0"Ta có
rj逢挨pi"vt·pj"Okejcgnku-Ogpvgp"pj逢"ucw"<
継 髪 鯨 継鯨華蝦 蝦 継 髪 鶏
E挨"ej院"p {"ej雨"8¿pi"mjk"m+2 << k-1."x噂k"m+1 n "j茨pi"u嘘"x壱p"v嘘e"rj違p"泳pi"vjw壱p"v衣q" rj泳e"GỤ"m-1<"j茨pi"u嘘"x壱p"v嘘e"rj違p"泳pi"ly rj泳e"GỤ"m+2 j茨pi"u嘘"x壱p"v嘘e"rj違p"泳pi"v衣q" u違p"rj育o"R"vƒk"v衣q"G0"" Km Vmax ½ Vmax V S
Hình 2.10: A瓜pi"j丑e"Okejcgnku-Menten<"v嘘e"8瓜"rj違p"泳pi"dcp"8亥w"ik違o"d噂v"
tjgq"]U̲"v<pi0
V (Velocity): v嘘e"8瓜."S (Substrate concentration)<"p欝pi"8瓜"e挨"ej医v
Swc"8欝"vj鵜"vc"vj医{"t茨pi"vtqpi"ikck"8q衣p"8亥w"p欝pi"8瓜"[S̲"e”p"vj医r"x "8cpiv<pi n‒p"e„"pij c"n "]GU̲"v<pi"mjk"x"8衣v"XM, V mj»pi"v<pi"p英c"fq"vq p"d瓜"G"荏"f衣pi"rj泳e" j嬰r"GU"*]GU̲?]GV̲+0
21
Rj逢挨pi"vt·pj"dk宇w"fk宇p"u詠"rj映"vjw瓜e"j茨pi"u嘘"x壱p"v嘘e"rj違p"泳pi"vjw壱p"v衣q"rj泳e" GU"x q"p欝pi"8瓜"e挨"ej医v"U.
懸 噺 撃兼欠捲"岷鯨峅
計警 髪 岷鯨峅
KM*j茨pi"u嘘"Okejcgnku-Ogpvgp+"e pi"pj臼"ƒk"n詠e"ik英c"G"x "U"e pi"n噂p."pij c"
là v rj違p"泳pi"e pi"n噂p
計暢 噺 "岷継峅岷鯨峅 岷継鯨峅
*]G̲"荏"f衣pi"v詠"fq="]U̲"e”p"vtqpi"fwpi"f鵜ej="]GU̲<"p欝pi"8瓜"n¿e"e¤p"d茨pi)
DＶpi"2.6: V pj"8員e"jk羽w"x噂k"e挨"ej医v"e栄c"c -Chymotrypsin và trypsin [4]
Enzyme Substrate kcat
(sec -1) Km (M) kcat / Km (M -1 sec-1) c-Chymotrypsin Trypsin Trypsin c-Chymotrypsin Trypsin c-Chymotrypsin c-Chymotrypsin
N-acetyl-L-tyrosine ethyl ester N-acetyl-L-tyrosine ethyl ester N-benzoyl-L-arginine ethyl ester N-benzoyl-L-arginine ethyl ester N-acetylglycine ethyl ester N-acetylglycine ethyl ester N-benzoylglycine ethyl ester
173a 14.5a 8.4a 1.4a 0.028b 0.066b 0.10c 3.2x10-3 4.2x10-2 1.0x10-5 1.5x10-2 0.79 0.41 2.3x10-3 5.4x104 3.45x102 8.4x105 9.3x101 3.5x10-2 1.6x10-1 4.3x101
+ Kcatvtqpi"rj違p"泳pi"GUå E+P 穴鶏
穴建 噺 懸 噺 倦頂銚痛岷継鯨峅
(ikƒ"vt鵜"e栄c"mecv"n "8挨p"x鵜"vj運k"ikcp, tính d茨pi"uge-1 ) + KM ?"ikƒ"vt鵜"n "p欝pi"8瓜"e挨"ej医v [S] = mol/L=M
Khi [S] =KM å懸 噺 蝶謎
態 (8員e"v pj"8瓜pi"n詠e"j丑e"e栄c"gp¦{og+
継鯨 蝦 継 髪 鯨 懸貸怠" 噺 倦貸怠岷継鯨峅
22
*V嘘e"8瓜"vj運k"ikcp"x"v pj"d茨pi"uge-1)
D違pi"p {"nói lên v pj"8員e"jk羽w"x噂k"e挨"ej医v"U"e栄c"hai enzyme trypsin và g-
ej{oqvt{rukp<"vt{rukp"e„"ƒk"n詠e"ecq"x噂k"pj„o"ctikpkpg"pj逢pi"t医v"vj医r"x噂k"o瓜v"czkv" cokp"vj挨o"(tyrosine+0"Vtƒk"n衣k."g- ej{oqvt{rukp"e„"ƒk"n詠e"t医v"ecq"x噂k"eƒe"czkv"cokp" vj挨o"*dgp¦q{nin{ekpg."v{tqukpg00+"x "8欝pi"vj運k"ej¿pi"vc"e pi"vj医{"v pj"8員e"jk羽w"e栄c"
trypukp"8嘘k"x噂k"ctikpkpg"n "t医v"ecq"x "e„"v pj"ik噂k"j衣p"j挨p"g- chymotrypsin. Trypsin
n "o瓜v"gp¦{og"8員e"vt逢pi"e栄c"eƒe"serine protease x "e„"xck"vt”"swcp"vt丑pi"vtqpi"8»pi" e亥o"oƒw0"
2.2.3. Vai trò và ho衣v"8瓜ng protease n丑c r逸n l映c 8嘘i v噂k"e挨"vj吋 b鵜 nhi宇m
8瓜c
Vj pj"rj亥p"ej pj"e栄c"p丑e"t逸p"n映e"dcq"i欝o<"
1. Go¦{og"n{"ik違k"rtqvgkp<"z¿e"vƒe"rjƒ"j栄{"protein e医w"vt¿e"o»"x "f磯p"8院p" 8cw."u逢pi"v衣k"x鵜"vt "e逸p0
2. Pj英pi"8瓜e"v嘘"rqlypeptid, phá j臼pi"f磯p"vtw{隠p"vj亥p"mkpj"x "e„"vj吋"f磯p"8院p" vt映{"vko"x "j»"j医r0"
3. Protease: phá x叡"eƒe"nk‒p"m院v"eƒe"rtqvgkp"rgrvkfg"vtqpi"o»."j壱w"sw違"i¤{" v鰻p"j衣k"8院p"vj pj"o衣ej"oƒw."zw医v"jw{院v."rjƒ"j栄{"e医w"vt¿e"u嬰k"e挨0
4. Phospholipase<"z¿e"vƒe"rj違p"泳pi"違pj"j逢荏pi"8院p"vj亥p"mkpj"x "e挨0"
5. Collagenase<"rjƒ"j栄{"eqnncigp"o»"nk‒p"m院v0
6. Eƒe"gp¦{og"ik嘘pi thrombin: zƒq"vt瓜p"e挨"ej院"e亥o"oƒw.
Vtk羽w"ej泳pi"pic{"x院v"t逸p"n映e"e逸p"rj映"vjw瓜e"x q"n逢嬰pi"8瓜e"mjk"d鵜"t逸p"e逸p0" Vtqpi"vt逢運pi"j嬰r"n逢嬰pi"8瓜e"pj姻, theo f k"vtk羽w"ej泳pi"pic{"v衣k"x鵜"vt "e逸p"dk吋w"jk羽p" u逢pi"8臼"x "x院v"oƒw"d亥ọ"mj»pi"dk吋w"jk羽p"vq p"vj¤p0" Vt逢運pi"j嬰r"n逢嬰pi"8瓜e"vtwpi"d·pj."vtk羽w"ej泳pi"dk吋w"jk羽p"pic{"v衣k"x鵜"vt "e逸p" u逢pi"t瓜r"ejk院o"rj亥p"n噂p"x́pi"d鵜"違pj"j逢荏pi0"Vtk羽w"ej泳pi"pjk宇o"8瓜e"vq p"vj¤p"zw医v" jk羽p."pj逢pi"mj»pi"違pj"j逢荏pi"8院p"v pj"o衣pi"*jw{院v"ƒr"ik違o"pj姻."vko"8壱r"pjcpj"x " vj荏"i医r+0 Vtqpi"vt逢運pi"j嬰r"pjk宇o"8瓜e"p員pị"vtk羽w"ej泳pidk吋w"jk羽p"jq p"vq p."ncp"pjcpj: rj́"p隠."zw医v"jw{院v"x "jq衣k"v穎"o»0"Vtk羽w"ej泳pi"pjk宇o"8瓜e"vq p"vj¤p"dk吋w"jk羽p."8cw"
23
d映pị"p»p"o穎c."jw{院v"ƒr"ik違o"jq p"vq p."vj荏"i医r."mj„"vj荏."pj鵜r"vko"8壱r"pjcpj"x " vtk羽w"ej泳pi"vj亥p"mkpj0"Piq k"tc"e”p e„"dk吋w"jk羽p"ej違{"oƒw"v瑛"x院v"e逸p"jq員e"d隠"o員v" pk‒o"o衣e0
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+ Jq衣v"j„c"hkdtkpqigp"vj pj"8挨p"x鵜hkdtkp0"A挨p"x鵜"hkdtkp"e„"8員e"v pj"v詠"nk‒p"m院v" x噂k"pjcw"swc"pj英pi"nk‒p"m院v"pj姻"8吋"m院v"j嬰r"vj pj"u嬰k"vt́pi"j嬰r"hkdtkp."e”p"vcp" vtqpi"f鵜ej0
+ Vjtqodkp"e pi"jq衣v"j„c"{院w"v嘘"ZKKK"vj pj"ZKKKc0"[院w"v嘘"ZKKKc"e„"jq衣v"v pj" vtcpuinwvcokpcug" x " v衣q" pj英pi" nk‒p" m院v" 8欝pi" j„c" vt鵜" p嘘k" eƒe" pj„o Q
*inwvcokpg+"x噂k"eƒe"pj„o"M"*n{ukpg+"ik英c"eƒe"u嬰k"vt́pi"j嬰r"hkdtkp."vj pj"o pi" n逢噂k" hkdtkp." j院v" vcp" 8逢嬰e" vtqpi" f鵜ej." iqo" eƒe" v院" oƒw" vj pj" jw{院v" mj嘘k" *vjtqodwụ"dnqqf"enqv+."e„"vj吋"n o"pij胤p"vw亥p"jq p"oƒw0
2.3.E愛"EJ蔭"Iå["NQ¡V"V萎K"EJ姥
2.3.1. H羽 th嘘ng huy院t m衣ch
J羽"vj嘘pi"jw{院v"o衣ej"i欝o"jck"vj pj"rj亥p"i逸p"nk隠p<"oƒw1jw{院v *rj映"n映e"KK+ x "n逢噂k" 嘘pi"o衣ej0"J羽"vj嘘pi"jw{院v"o衣ej"rj栄"vq p"d瓜"e挨"vj吋"x "zgp"m胤"u¤w"x q"eƒe"o»0
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U詠"8»pi"oƒw"n "o瓜v"j羽"vj嘘pi"8«"8逢嬰e"j·pj"vj pj"mj»pi"8吋"o医v"oƒw"eƒej"d育o"sinh,
rj泳ev衣r"j挨p"e挨"ej院"e亥o"oƒw"p瓜k"v衣k."x·"e„"rj嘘k"j嬰r"x噂k"u詠"mj荏k"8瓜pi"o瓜v"u嘘"e挨"ej院" ej嘘pi"pjk宇o"mjw育p0"Vtqpi"vt逢運pi"j嬰r"d鵜"ej医p"vj逢挨pi"o荏."mj»pi"v詠"pjk‒p."oƒw"tc" piq k"jw{院v"o衣ej."t欝k"8»pi"n衣k"pic{"vt‒p"fc0"U詠"8»pi"oƒw"piq k"e挨"vj吋"p {"8逢嬰e"mj荏k" 8瓜pi"x噂k"o瓜v"u嘘"{院w"v嘘"8«"8逢嬰e"dk院v"n "fq"o瓜v"d隠"o員v"m院v"j嬰r"x噂k"dc"vj pj"rj亥p"e栄c" oƒw<" {院w" v嘘" ZKK." rtgmcnnkmtgkp" x " mkpkpqigp" e„" vt丑pi" n逢嬰pi" rj¤p" v穎" ecq" *JOY" mkpkpqigp."JOYM+0"D違p"ej医v"e栄c"d隠"o員v"8«"8逢嬰e"dk院v"n "fq"pj英pi"8k吋o"e„"v pj"8k羽p" ¤ọ"x·"vtqpi"e挨"vj吋"*kp"xkxq+"mjk"vk吋w"e亥w"vk院v"tc"rqn{rjqurjcvg."ej医v"p {"jq衣v"j„c"{院w"
24
v嘘"ZKK"vj pj"ZKKc0"Eƒe"rjqurjcvcugu"vtqpi"e挨"vj吋"pi逢嬰e"n衣k"n o"o医v"jk羽w"泳pi"8»pi" oƒw"e栄c"rqn{rjqurjcvg0"Ak隠w"e pi"8«"dk院v"8逢嬰e"n "荏"pj英pi"pi逢運k"vjk院w"j映v"u詠"dk吋w" jk羽p"e栄c"dc"rtqvgkp"p‒w"vt‒p."u詠"e亥o"oƒw"p瓜k"v衣k"*mj荏k"8瓜pi"x噂k"{院w"v嘘"TF và VIIa) x磯p"fk宇p"dk院p"d·pj"vj逢運pị"v泳e"{院w"v嘘"ZKKc"n "mj»pi"e亥p"vjk院v"ejq"u詠"e亥o"oƒw"p瓜k"v衣k0" Jck"{院w"v嘘"XKKc"x "ZKKc"mj荏k"8瓜pi"8»pi"oƒw"eƒej"8瓜e"n壱r0 [院w"v嘘"ZKK"n "o瓜v"rtqvgkp":2mF."i欝o"o瓜v"ejw鰻k"p員pi"*575cc+"x "o瓜v"ejw鰻k" pj姻"*465cc+"nk‒p"m院v"x噂k"pjcw"swc"o瓜v"e亥w"fkuwnhkfg0"[院w"v嘘"ZKK"jq衣v"j„c"*ZKKc+"e„" jq衣v"v pj"e栄c"o瓜v"ugtkpg"gpfqrgrvkfcug."vtwpi"v¤o"z¿e"vƒe"p茨o"vt‒p"ejw鰻k"pj姻"e栄c" rj¤p"v穎0"ZKK"v詠"jq衣v"m„c"vj pj"ZKKc."v泳e"ZKKc"jq衣v"j„c"ZKK"mjk"i員r"o瓜v"u嘘"x壱v"nk羽w" pj逢"vj栄{"vkpj."vj衣ej"ecq."fgzvtcp"uwnhcvg."piw{‒p"eqnncigp."jq員e"rqn{rjqurjcvg0"A吋" ej院"v衣q"x "rjƒv"vtk吋p"eƒe"x壱v"nk羽w"u穎"f映pi"ejq"d羽pj"pj¤p"vko"o衣ej."u詠"jq衣v"j„c"{院w" v嘘"ZKK"8cpi"8逢嬰e"pijk‒p"e泳w"u¤w"j挨p"x隠"e挨"ej院"j„c"n#"e栄c"u詠"jq衣v"j„c0"[院w"v嘘"ZKKc" c”p"vjco"ikc"8k隠w"vk院v"o瓜v"u嘘"jq衣v"8瓜pi"ukpj"n#."jq衣v"j„c"8院p"p<o"vk隠p"rtqvgcug"e栄c jw{院v"v逢挨pi<"rtgmcnnkmtgkp."{院w"v嘘"ZK."{院w"v嘘"XKK."rncuokpqigp"x "d鰻"vj吋"E3."o瓜v" vj pj"rj亥p"vtqpi"j羽"vj嘘pi"ej嘘pi"pjk宇o"d育o"ukpj0 Pjk宇o"mjw育p"i¤{"xk‒o Hình 2.11: Jq衣v"8瓜pi"e栄c"dtcf{mkpkp [49] Pj逢"8«"p„k"vt‒p."rtgmcnnkmtgkp"x "JOYM"n "jck"8欝pi"{院w"v嘘"e栄c"ZKKc"vtqpi"u詠"mj荏k" 8瓜pi"8»pi"oƒw"mjk"e„"ej医p"vj逢挨pi"o荏0"Jck"8欝pi"{院w"v嘘"p {"vjw瓜e"j羽"vj嘘pi"mkpkp." j羽"vj嘘pi"i欝o"o瓜v"u嘘"rtqvgkp"e„"o員v"vtqpi"oƒw"x "vt‒p"o pi"v院"d q"p瓜k"o»"*mkpkp- kallikrein system, KKS) [37]0"Pic{"ucw"mj荏k"8瓜pi"8»pi"oƒw."jck"8欝pi"{院w"v嘘"p {"8k" x q"jq衣v"8瓜pi"vtqpi"eƒe"e挨"ej院"i¤{"xk‒ọ"8k隠w"j pj"jw{院v"ƒr."8»pi"oƒw"x "i¤{"8cw." n "pj英pi"vtk羽w"ej泳pi"mflo"vjgq"ucw"vj逢挨pi"v ej"*pj逢"d鵜"d臼pị"xk‒o"fq"pjk宇o"mjw育p."
25
u嘘ẹ"f鵜"泳pi+0"Vtqpi"eƒe"v鰻p"vj逢挨pi"p {"e„"o»"x "v院"d q"d鵜"j逢"j臼pị"zw医v"jw{院v."n " pj英pi"e挨j瓜k"i¤{"pjk宇o"mjw育p0"Hình 2.11 ejq"vj医{"ZKKc"z¿e"vƒe"u違p"zw医v"mcnnkmtgkp" *jq衣v"hóa prekallikrein) và tk院r"vjgq"n "u詠"mjw院ej"8衣k"u違p"zw医v"dtcf{mkpkp"*DF+"v瑛" OYM0"Mkpkpqigp"vt丑pi"n逢嬰pi"rj¤p"v穎"vj医r"*NOYM+"ejq"vj pj"rj育o"mcnnkfkp"*MF."
không nêu trên hình 2.11+0"Rtgmcnnkmtgkp"x "JOYM"fq"icp"vk院v"tc."8逢c"x q"oƒw0" NOYM"x "mcnnkmtgkp"8逢嬰e"u違p"zw医v"v衣k"ej厩0"Mcnnkmtgkp"e„"jq衣v"v pj"e栄c"o瓜v"ugtkpg" rtqvgcug."ik違k"rj„pi"tc"DF"x "MF"v瑛"eƒe"vk隠p"rtqvgkp"*M+0"DF"n "o瓜v"pcpqrgrvkfg"e„" ctikpkpg"荏"jck"8亥w"*T1PPGFSPFR9+"x "MF"n "DF"x噂k"o瓜v"8挨p"x鵜"n{ukpg"vt逢噂e"ctikpkpg" 8亥w"P"ew嘘k"*MTRRIHURHT+0"Eƒe"cokpqrgrvkfcug"ejw{吋p"jóa KD thành BD. Các
gpfqrgrvkfcug"rj¤p"j栄{"DF"i丑k"n "eƒe"mkpkpcug<"*3+"Cpikqvgpukp-converting enzyme
*CEG+"vj栄{"rj¤p"DF"荏"nk‒p"m院v"rgrvkfg"9-:="CEG"e”p"8逢嬰e"i丑k"n "mkpkpcug"KK0"*4+" Cokpqrgrvkfcug"R"*CRR+"e逸v"nk‒p"m院v"3-40"*5+"Ectdqz{rgrvkfcug"P"*ERP+"e逸v"nk‒p"m院v"
8-;"*P"n "f衣pi"gp¦{og"n逢w"j pj"vtqpi"oƒw="ectdqz{rgrvkfcug"O"n "f衣pi"nk‒p"m院v"vt‒p" o pi"v院"d q."jq衣v"8瓜pi"v衣k"ej厩+0"Fq"jq衣v"8瓜pi"rj¤p"j栄{"e栄c"ej¿pị"eƒe"gpfqrgrvkfcug" p {"j衣"p欝pi"8瓜"DF."ik違o"vƒe"8瓜pi"e栄c"DF"x q"eƒe"vj映 vj吋"D4"x "D3"e栄c"p„"*Hình 2.11).
DF"e„"jq衣v"v pj"n o"ik«p"jw{院v"o衣ej"x "n o"v<pi"v pj"vj医o"e栄c"x pj"o衣ej="fq"8„" n o"j衣"jw{院v"ƒr"*j{rqvgpukxg+."i¤{"rj́"x "o瓜v"u嘘"jq衣v"v pj"mjƒe"8«"8逢嬰e"mjck"vjƒe" pjk隠w"vtqpi"f逢嬰e"j丑e0"U詠"mjƒo"rjƒ"tc"DF"e„"nk‒p"swcp"8院p"p丑e"t逸p"8瓜e"*Dqvjtqru"
jararaca, Brc¦kn." Ocwt ekq" Tqejc" g" Uknxc." 3;6:+" x " eƒe" f逢嬰e" rj育o" p瓜k" ukpj" *cwvqrjctoceqnqikecn"uwduvcpegu1gpfqigpqwu"cwvceqkfư0"V瑛"pj英pi"p<o"3;5;"Tqejc" g"Uknxc"8«"pijk‒p"e泳w"x隠"u詠"i¤{"u嘘e"vw亥p"jq p"*ektewncvqt{"ujqem+"mjk"d鵜"pjk宇o"8瓜e" p丑e"t逸p"vjw瓜e"f”pi"Òt逸p"n映eÓ"*viperidae). (Vtqpi"f”pi"t逸p"p {"e„"pjk隠w"nq k"e„"o w" p¤w."8員e"dk羽v"pj英pi"nq k"e„"j嘘"oƒ."rkv"xkrgt0"V瑛"ÒxkrgtÓ"mj»pi"e„"p瓜k"fwpi"Òo w"n映eÓ" o "n "v瑛"t¿v"i丑p"e栄c"jck"v瑛"nc-tinh vivo (tôk"u嘘pi+"x "pario *v»k"u違p"ukpj+0"P衣p"pj¤p"d鵜" t逸p"8瓜e"f”pi"pj叡p"m pj"*elapidae+"mj»pi"dcq"ik運"d鵜"u嘘e"vw亥p"jq p0"Pj逢pi"mjk"d鵜"o瓜v" t逸p"vjw瓜e"f”pi"viperidae e逸p."d羽pj"pj¤p"jc{"d鵜"u嘘e"vw亥p"jq p"x "rj́"v衣k"ej厩0"X q" p<o"3;6:."o瓜v"vj穎"pijk羽o"ejq"p丑e"Bothrops jararaca x q"jw{院v"vjcpj"n o"p欝pi"8瓜" dtcf{mkpkp"v<pi"n‒p0"V瑛"dtcf{mkpkp"n "v瑛"ijfir"e栄c"jck"v瑛"J{"n衣r"brady e„"pij c"n " ej壱o"x "kini pij c"n "fk"8瓜pi"x·"pj壱p"vj医{"tw瓜v"pqp"d羽pj"pj¤p"pjk宇o"8丑e"t逸p"eq."fk"
26
8瓜pi"ej壱o0"Vk院r"8„"dtcf{mkpkp"8逢嬰e"zƒe"8鵜pj"n o"ik«p"jw{院v"o衣ej."ik違k"vj ej"e挨"ej院" e栄c"eƒe"vtk羽w"ej泳pi"pj壱p"vj医{0"O瓜v"u嘘"rtqvgcug"x "rgptidase e pi"8«"8逢嬰e"v·o"vj医{" vtqpi"eƒe"p丑e"t逸p"8瓜e"vjw瓜e"f”pi"viperidae0"ÒT逸p"n映eÓ"e逸p"e”p"e„"vj吋"f磯p"8院p"uw{" vj壱p"fq"eƒe"gp¦{og"vj栄{"rj¤p"rtqvgkp"e栄c"p丑e"i¤{"jq衣k"v穎"v院"d q"x "o»"e栄c"v鰻"ej泳e" eƒe" 嘘pi" n丑e" vtqpi" vj壱p" *inqogtwnk+." vtqpi" n¿e" mcnk" jw{院v" v<pi" *j壱w" sw違" e栄c" v<pi" dtcf{mkpkp+."jgoqinqdkp"x "o{qinqdkp"pk羽w"e pi"v<pi [20].
G-rtqvgkp"x "u詠 ttw{隠p"v p"jk羽w"swc"o pi"v院"d q
Dtcf{mkpkp"vƒe"8瓜pi"x q"jck"vj映"vj吋"D4"x "D3"e„"o員v"vt‒p"j亥w"j院v"eƒe"nq衣k"v院"d q" vtqpi"e挨"vj吋0"Mjk"nk‒p"m院v"x q"jck"vj映"vj吋"8„"DF"m ej"8瓜pi"pjk隠w"jq衣v"8瓜pi"ukpj"n#" e栄c"eƒe"v院"d q"ej泳e"p<pi<"v<pi"8瓜"vj医o"x pj"o衣ej."ik«p"e挨"vt挨p"vk吋w"v pj"o衣ej."j衣" jw{院v"ƒr."eq"e挨"vt挨p"tw瓜v."eq"e挨"vt挨p"8逢運pi"j»"j医r"*v衣q"v pj"d隠p+."m ej"vj ej"v院"d q" vj亥p"mkpj"ikƒe"swcp"*v<pi"mj違"p<pi"e違o"pj壱p"8cw"8噂p+."i¤{"t嘘k"u詠"vk院v"eƒe"kqp"e栄c"eƒe" v院" d q" dk吋w" o»." m ej" vj ej" d衣ej" e亥w" vk院v" e{vqmkpg." PQ." m eh thej" v鰻pi" j嬰r"
prostaglandin.. A„"n "pj英pi"8ƒr"泳pi"ukpj"j丑e"*ukpj"n#1ok宇p"pjk宇o"d育o"ukpj+"n o" v<pi"u詠"ejw{吋p"x壱p"e栄c"jw{院v"v逢挨pi"x "u詠"fk"ejw{吋p"e栄c"eƒe"v院"d q"oƒw0
Jck"vj映"vj吋"D4"x "D3"e栄c"dtcf{mkpkp"n "pj英pi"rtqvgkp"vq p"vcp"vtqpi"o pị"zw{‒p" o pi"v院"d q"sua l衣k"d違{n亥p."8亥w"P"ew嘘k"e栄c"rj¤p"v穎"p茨o"piq k"v院"d q"8吋"e違o"pj壱p" p欝pi"8瓜"rj嘘k"v穎"DF"vtqpi"oƒw"x "rj亥p"E"ew嘘k"e栄c"rtqvgkp"p茨o"vtqpi"v院"d q."nk‒p"m院v" x噂k"rj泳e"j嬰r"I-rtqvgkp="rj亥p"vtqpi"v院"d q"e„"o員v"e栄c"ugtkpg."vjtgqpkpg"x "v{tqukpg" 8吋"e„"vj吋"v衣q"nk‒p"m院vguvgt"x噂k"pj„o"rjqurjqt{n0"Eƒe"I-protein có vai trò trung gian
vtw{隠p"v p"jk羽w"swc"o pi"v院"d q"*ukipcn"vtcpufwevkqp+0"U詠"nk‒p"m院v"x噂k"rj嘘k"v穎"d‒p" piq k"v院"d q"n "o瓜v"v p"jk羽w"8逢嬰e"vtw{隠p"zw{‒p"o pi"v院"d q"x q"8院p"8挨p"x鵜"g"thành
rj亥p"e栄c"I-rtqvgkp."vk院r"vjeo Ggd逸v"IVR"x "jq衣v"j„c"mj荏k"8瓜pi"eƒe"8ƒr"泳pi"e栄c"v院" d q0" A挨p" x鵜" g" e栄c" I-rtqvgkp" e„" jq衣v" v pj" e栄c" o瓜v" IVRcug" *nk‒p" m院v" x噂k" IVR." iwcpqukpg"vtkrjqurjcvg+="jq衣v"8瓜pi"e栄c"I-rtqvgkp"8k隠w"j”c"eƒe"{院w"v嘘"ukpj"n#"x "n羽" vjw瓜e"x q"p欝pi"8瓜"e栄c"IVR"vtqpi"v院"d q0"G-rtqvgkp"jq衣v"8瓜pi"pj逢"o瓜v"p¿v"v逸v"d壱v." d壱v"mjk"IVR"i逸p"x q"x "v逸v"mjk"e„"IFR"i逸p"nk隠p0
Vj映"vj吋"D4"8逢嬰e"dk吋w"jk羽p"rj鰻"dk院p"vt‒p"pjk隠w"nq衣k"v院"d qej泳c"p<pi vtqpi"e挨"vj吋"x " n "vj pj"rj亥p"e医w"vj pj"e栄c"o pi"v院"d q"d·pj"vj逢運pi"x "mj荏k"8瓜pi"pjk隠w"jq衣v"8瓜pi: kej"vj ej"rjqurjqnkrcug"E"8吋"n o"v<pi"p欝pi"8瓜"Ec++ p瓜k"d q"x "泳e"ej院"cfgp{ncvg"
27
e{encug"*泳e"ej院"u詠"u違p"zw医v"eCOR."cfgpqukpg"oqpqrjqurjcvg"x”pị"rj¤p"v穎"v p"jk羽w" vj泳+0"Vj映"vj吋"D4"e”p"m ej"8瓜pi"u詠"ikƒp"rj¤p"v院"d q"swc"8逢運pi"jq衣v"j„c"rtqvgkp" mkpcug0"Vj映"swcp"D3"ej雨"8逢嬰e"dk吋w"jk羽p"mjk"e„"xk‒ọ"ej医p"vj逢挨pị"d鵜"d臼pị"u嘘e"jq員e" f鵜"泳pi0"D3"e pi"jq衣v"8瓜pi"n o"v<pi"Ec++ p瓜k"d q0"U詠"zw医v"jk羽p"e栄c"D3"vt‒p"v院"d q" e pi"n "j壱w"sw違"e栄c"pjk宇o"mjw育p"o«p"v pj0"Jck"vj映"vj吋"e栄c"dtcf{mkpkp"nk‒p"m院v"x噂k"
G-rtqvgkp"8違o"pjk羽o"ej泳e"p<pi"8k隠w"vk院v"u詠"e亥o"oƒw."e¤p"d茨pi"vj栄{"f鵜ej"e栄c"v院"d q0" 雲"rj亥p"8亥w"E"ew嘘k"e栄c"vj映"vj吋"D4"v院"d q"vj壱p."e„"o瓜v"8q衣p"8員e"vt逢pi"ocpi"8挨p"x鵜"
tyrosine-rjqurjqt{n"i丑k"n "KVKO"*koowpqtgegrvqt"v{tqukpg-based inhibitory motif,
vj映"vj吋"泳e"ej院"jq衣v"8瓜pi"ok宇p"swc"8挨p"x鵜V[T+"vj逢運pi"e„"o員v"vt‒p"eƒe"vj映"vj吋"e栄c" eƒe"v院"d q"ok宇p"pjk宇o"jq衣v"8瓜pi"泳e"ej院"8ƒr"泳pi"mjk"j院v"e亥p"vjk院v0"U詠"e„"o員v"e栄c" vt·pj"v詠"KVKO"ejq"jk吋w"n "vj映"vj吋"D4"8逢嬰e" o瓜v"rjqurjcvcug"8員e" jk羽w"x噂k"rtqvgkp" v{tqukpg"vt詠e"vk院r"vƒe"8瓜pi"8吋"8k隠w"vk院v."ik噂k"j衣p"jk羽w"n詠e"jq衣v"8瓜pi"e栄c"dtcf{mkpkp0 Épi"x噂k"vj映"vj吋"e栄c"dtcf{mkpkp."e”p"pjk隠w"nq衣k"vj映"vj吋"mjƒe"vt‒p"o瓜v"v院"d q"8吋"e違o" pj壱p"eƒe"rj¤p"v穎"ej泳e"p<pi"mjƒe"vtqpi"oƒw0"A嘘k"x噂k"eƒe"v院"d q"ok宇p"pjk宇ọ"u詠"fk" 8瓜pi"8院p"x鵜"vt "e„"pjk宇o"mjw育p"jc{"fk"x q"o瓜v"x鵜"vt "8鵜pj"e逢"vrong j衣ej."v院"d q"8鵜pj" j逢噂pi"fk"vjgq"u詠"dk院p"8瓜pi"p欝pi"8瓜"*itcfkgpv+"e栄c"eƒe"rgrvkfg"ej泳e"p<pi"i丑k"n " ejgoqmkpg."rgrvkfg"j„c"j逢噂pi"8瓜pi0"Vt‒p"eƒe"v院"d q"ok宇p"pjk宇o"e„"eƒe"vj映"vj吋"8員e" jk羽w"x噂k"eƒe"ejgoqmkpg"p {0"Vtqpi"jq衣v"8瓜pi"e栄c"eƒe"vj映"vj吋"dtcf{mkpkp"e„ u詠"rj嘘k" j嬰r"x噂k"eƒe"vj映"vj吋"e栄c"e栄c"eƒe"ejgoqmkpg"x "eƒe"vj映"vj吋"e栄c"eƒe"rgrvkfg"vtqpi"j羽" vj嘘pi"tgpkp-angiotensin (RAS, renin-cpikqvgpukp"u{uvgợ"swc"mj違"p<pi"nk‒p"m院v"ik英c" vj映"vj吋"D4"x噂k"gp¦{og"CEG"pj逢"8«"p„k"vt‒p0"Eƒe"rj嘘k"j嬰r"jq衣v"8瓜pi"ik英c"eƒe"nq衣k"
tj映"vj吋"8„"8«"8逢嬰e"i丑k"n "eƒe"Ò8 o"rjƒpÓ"ik英c"eƒe"vj映"vj吋"*etquu-talk). Cáe"jq衣v"8瓜pi" ukpj" j丑e" p {" 8«" vjw" j¿v" u詠" n逢w" v¤o" t医v" n噂p" e栄c" eƒe" pijk‒p" e泳w" f逢嬰e" j丑e0"
Apikqvgpukpqigp"8逢嬰e"icp"vk院v"tc."8逢c"x q"oƒw."vk隠p"vj¤p"e栄c"pjk隠w"f衣pi"cpikqvgpukp0" V院"d q"vj壱p"ukpj"tc"o瓜v"rtqvgcug"i丑k"n "tgpkp."8k"x q"oƒw"vw亥p"jq p"x "ik違k"rj„pi"tc" cpikqvgpukp"K"v瑛"cpikqvgpukpqigp0"CEG"ejw{吋p"cpikqvgpukp"K"vj pj"cpikqvgpukp"KK0" Cpikqvgpukp" KK" n o" eq" jw{院v" o衣ej." n o" v<pi" jw{院v" ƒr." pi逢嬰e" x噂k" jk羽w" 泳pi" e栄c"
bradykinin.
Eƒe"vj映"vj吋"nk‒pm院v"x噂k"I-protein (G-rtqvgkp"eqwrngf"tgegrvqt."IRET+"ej雨"e„"o員v"荏" eƒe"v院"d q"e„"pj¤p"vj壱v"*gwmct{qvg+."pj逢pi"t医v"rj鰻"dk院p"v瑛"xk"p医o"8院p"v院"d q"8瓜pi"x壱v"
28
e„"z逢挨pi"u嘘pi0"Eƒe"rj嘘k"v穎"e栄c"eƒe"vj映"vj吋"p {"e„"vj吋"n "pj英pi"rj¤p"v穎"ók"x鵜."eƒe" rj¤p"v穎"dƒq"jk羽w"ik噂i tính (pheromone), các hóc-o»p."eƒe"rj¤p"v穎"vtw{隠p"v p"jk羽w" ik英c"v院"d q"vj亥p"mkpj"*pgwtqvtcpuokvvgt+0"Eƒe"rj嘘k"v穎"e栄c"eƒe"vj映"vj吋"nk‒p"m院v"x噂k"I-
rtqvgkp"e„"vj吋"n "pj英pi"rj¤p"v穎"pj臼."pj英pi"rgrvkfg."jq員e"o瓜v"rtqvgkp"n噂p."ej¿pi"8隠w" e„"pj英pi"xck"vt”"pj医v"8鵜pj vtqpi"u詠"sw{院v"8鵜pj"eƒe"jq衣v"8瓜pi"ukpj"j丑e0"Eƒe"vj映"vj吋" e違o"pj壱p"ƒpj"uƒpi"*rjqvqp+"vt‒p"eƒe"v院"d q"vj鵜"ikƒe"e pi"n "pj英pi"vj映"vj吋"i逸p"nk隠p" x噂k"I-protein.
E挨"ej院"n o"vcp"mj嘘k"jw{院v
Mjk"d鵜"ej医p"vj逢挨pi"o荏."p院w"e„"mjw育p"pjk宇ọ"o瓜v"piw{"e挨"rj鰻"dk院p"e„"vj吋"z違{" tc"n "pjk宇o"p瓜k"8瓜e"v嘘"*gpfqvqzkpư"jq員e"nkrkf"C."o瓜v"vj pj"rj亥p"e栄c"p瓜k"8瓜e"v嘘0" Pj英pi"o違pj"x映p"e栄c"x臼"eƒe"mjw育p"Itco"¤o"p {"e„"mj違"p<pi"jq衣v"j„c"{院w"v嘘"ZKK" pj逢" rqn{rjqurjcvg" e栄c" vk吋w" e亥w0" Ak隠w" p {" i¤{" 8»pi" oƒw" v pj" o衣ej" *xgpqwu" vjtqodqukư0""Pj逢pi"vtqpi"j羽"vj嘘pi"jw{院v"o衣ej"vjk院v"n壱r"u印p"e„"pj英pi"vj pj"rj亥p"8吋" d違q"8違o"u詠"vcp"mj嘘k"jw{院v"*hkdtkpqn{ukự"鰻p"8鵜pj"n衣k"j羽"vj嘘pi"huy院v"o衣ej"x "u詠"e亥o"
máu (Hình 2.12). U詠"vcp"mj嘘k"jw{院v"ej栄"{院w"n "rj¤p"j栄{."n o"vcp"n逢噂k"hkdtkp"8«"Ò鰻p" 8鵜pjÓ0"A吋"vj詠e"jk羽p"ej泳e"p<pi"8„."oƒw"8«"8逢嬰e"e医w"vj pj"x噂k"o瓜v"rj¤p"v穎"swcp"vt丑pi" i丑k"n "rncuokpqigp"*RNI+0"RNI"ej栄"{院w"8逢嬰e"icp"ewpi"e医r."pj逢pi"vj逢嬰pi"vj壱p."vj壱p." p«q."vkpj"jq p."vkọ"rj鰻k."v穎"ewpi"nƒej."vw{院p"泳ẹ"tw瓜v"8隠w"8«"8逢嬰e"zƒe"8鵜pj"n "e„"v鰻pi" j嬰r"RNI0
Rtqvgkp"p {"n逢w"j pj"vtqpi" oƒw"荏"jck"f衣pi<" f衣pi"i丑k"n "K"ocpi"jck"pj„o" in{equ{n"*i逸p"vt‒p"P"e栄c"Cur4:;"x "vt‒p"Q"e栄c"V{t568+"e”p"f衣pi"KK"n衣k"ocpi"ej雨"o瓜v"
nhóm glycosyl (trên Tyr346). Fq"ocpi"jq衣v"v pj"vjk院v"{院w"n "n o"vcp"jw{院v"mj嘘k."RNI" 8«"8逢嬰e"pj壱p"vj医{"e„"nk‒p"ecp"8院p"d羽pj"n#<"zw医v"jw{院v."vƒk"v衣q"v鰻p"vj逢挨pị"d羽pj"vkọ" 8瓜v" sw液" x " wpi" vj逢0" RNI" n " vk隠p" vj¤p" e栄c" jck" ukpj" rj育o" swcp" vt丑pi<" rncuokp" x "
angiostatin. Rncuokp"n "o瓜v"ugtkpg"rtqvgcug"jq衣v"8瓜pi"n o"vcp"jw{院v"mj嘘k"*hkdtkpqn{ukư" x "jq衣v"8瓜pi"vtqpi"u詠"vƒk"v衣q"v鰻p"vj逢挨pi"*yqwpf"tgoqfgnkpi+0
Rj¤p"v穎"8逢嬰e"dk吋w"jk羽p"dcp"8亥w"i欝o":32"8挨p"x鵜"czkv"cokp."rgrvkfg"v p"jk羽w" f磯p"8亥w"i欝o"3;"8挨p"x鵜"vƒej"tc."rtqvgkp"jq p"vjk羽p"i欝o"9;3"cz v"cokp."x噂k"o瓜v"u嘘"8挨p" x鵜" ocpi" in{equ{n" x " rjqurjqt{n0" Piw{‒p" rncuokpqigp" i丑k" n " Inw-plasminogen (Glu1-Cup9;3+0"Rncuokp"nq衣k"vt瑛"rgrvkfg"8亥w"i丑k"n "rgrvkfg"jq衣v"j„c"*Inw3-Lys77),
29
rj亥p" e”p" n衣k" i丑k" n " N{u-plasminogen (Lys78-Asn791) (hình 2.13)0" F衣pi" N{u-
rncuokpqigp"f宇"jq衣v"j„c"vj pj"rncuokp"j挨p"f衣pi"piw{‒p"Inw-plasminogen.
Hình 2.12: E挨"ej院"vcp"mj嘘k"jw{院v [50] Hình 2.13: E医w"vt¿e"d壱v"o瓜v"*vt·pj"v詠+" e栄c"rncuokpqigp"pi逢運k [52]
Cpikquvcvkp"泳e"ej院"jq衣v"8瓜pi"ukpj"n逢噂k"o衣ejo噂k*cpikqigpguku"kpjkdkvqt+"fk宇p" tc"vtqpi"u詠"rjƒv"vtk吋p"eƒe"nq衣k"mj嘘k"w."8吋"oƒw"pw»k"f逢叡pi"v院"d q"e栄c"v鰻"ej泳e"mj嘘k"w x "o»"vƒk"v衣q.
Mjk"8«"dƒo"x q"o pi"v院"d q"jc{"x q"mj嘘k"jw{院v."rj¤p"v穎"rncuokpqigp"ejw{吋p" vj pj"o瓜v"f衣pi"o荏"tc"f宇"j挨p"ejq"u詠"jq衣v"j„c"uq"x噂k"f衣pi"n逢w"j pj"iqo"n衣k"ej員v"ej胤0" U嘘"eƒe"rtqvgcug"e„"vj吋"jq衣v"j„c"RNI"vtqpi"eƒe"8k隠w"mk羽p"ukpj"n#"n <"rtqvgcug"o»"jq衣v"
hóa plasminogen (tissue plasminogen activator, tPA), wtqmkpcug" jq衣v" j„c"
plasminogen (urokinase plasminogen activator, uPA), kallikrein."{院w"v嘘"ZKc"x "ZKKc"
(Hình 2.12). [院w"v嘘"ZKKc"jq衣v"j„c"RNI"vj pj"rncuokp0"Rncuokpqigp"KK"vj逢運pi"jc{" dƒo"nk隠p"vt‒p"d隠"o員v"eƒe"v院"d q."rncuokpqigp"K"n逢w"j pj"pjk隠w"j挨p"vtqpg máu nên
8逢嬰e"i逸p"pjk隠w"j挨p"x q"mj嘘k"jw{院v"mjk"mj嘘k"jw{院v"zw医v"jk羽p0
V鰻"ej泳e"rj¤p"v穎"RNI"ejq"vj医{"i欝o"d違{"x́pi"*J·pj"4036+0"Piw{‒p"rj¤p"v穎" i欝o"9;3"8挨p"x鵜."i丑k"n "Inw-plasminogen (Glu1-Asn 791+0"RNI"o医v"8k"o瓜v"8q衣p"8亥w"-
PJ4."99"8挨p"x鵜"i丑k"n "N{u-plasminogen (Lys78-Asn791). Glu-PLG và Lys-PLG có
f衣pi"mjƒe"dk羽v"pjcw.u詠"jq衣v"j„c"N{u-RNI"v衣q"rncuokp"pjcpj"j挨p"uq"x噂k"u詠"jq衣v"j„c"
Glu-RNI0"Rj亥p"rgrvkfg"8亥w"i欝o"99"8挨p"x鵜"*PJ2Glu1-Lys77."i丑k"n "AP, activation
30
rgrvkfg+."vk院r"vjgq"n "p<o"rj亥p"M."fq"e„"dc"nk‒p"m院v"-S-S- vtqpi"o厩k"x́pi"K p‒p"p<o" x́pi"M"e„"f衣pi"vt”p"pj逢"eƒk"dƒpj"*mtkping+."vk院r"8院p"n "rj亥p"EN"*engcxcig1cevkxcvkqp" nqqr+"x "rj亥p"ew嘘k"SP ocpi"jq衣v"v pj"Ugtkpg"Rtqvgcug"e栄c"Rncuokp0"Vtqpi"8q衣p"EN"
có liên m院v"rgrvkfg"Cti561-Val562 (fiCS561/2 trên Hình 2.14) n "x鵜"vt "jq衣v"j„c"RNI" vj pj"rncuokp="UR"mj荏k"8亥w"x噂k"8挨p"x鵜"Xcn562."e„"rj亥p"8亥w"rj栄"vt́o"n‒p"rj亥p"EN0" Vtqpi"8k隠w"mk羽p"ukpj"n#"*kp"xkxq+"v鰻"ej泳e"ecq"j挨p"e栄c"rj¤p"v穎"RNI"u逸r"8員v"eƒe"x́pi" 8吋"e„"vj吋"nk‒p"m院v"x噂k"pjk隠w"nq衣k"e挨"ej医v"mjƒe"pjcw"vtqpi"jq衣v"8瓜pi<"rj¤p"v穎"n噂p"vcp" vtqpi"f鵜ej"pj逢"rtqvgkp."d隠"o員v"v院"d q."x "pj英pi"rj¤p"v穎"pj臼"pj逢"n{ukpgÈJq衣v"8瓜pi" rncuokp"vjw瓜e"x́pi"EN"x "UR0"Eƒe"x́pi"M3"8院p"M6"8違o"d違q"jq衣v"8瓜pi"cpikquvcvkp0 Hình 2.14: V鰻"ej泳e"rj¤p"v穎"RNI"i欝o"9"x́pi [48] A吋"mj荏k"8瓜pi"u詠"rj¤p"j栄{"n o"vcp"mj嘘k"jw{院v."u詠"jq衣v"j„c"e亥p"nk‒p"m院v"vj pj" rj泳e"j嬰r"dc"vj pj"rj亥p."RNỊ"hkdtkp"x "vRC0"Vtqpi"eƒe"jq衣v"j„c"ukpj"n# khác liên
ecp"x噂k"u詠"fk"ejw{吋p"v院"d q"x "vƒk"v衣q"v鰻p"vj逢挨pị"wRC"i逸p"x q"vj映"vj吋"wRCT"*wRC" Tgegrvqt+"x "RNI"i逸p"x q"rj泳e"j嬰r"8„0 Mjk"mj嘘k"jw{院v"8«"vcp."rncuokp"ik違k"rj„pi" tc"m院v"j嬰r"pic{"x噂k"g4-cpvkrncuokp"u印p"e„"vtqpi"jw{院v"v逢挨pi"x "d鵜"d医v"jq衣v."mj»pi"
chq"rncuokp"rj¤p"j栄{"hkdtkpqigp"jw{院v."n o"ik違o"p欝pi"8瓜"e栄c"vj pj"rj亥p"p {0 Jck"rtqvgcug"vRC"x "wRC"8隠w"e逸v"RNI"荏"nk‒p"m院v"Cti561-Val562 8吋"ik違k"rj„pi" e医w"vt¿e"RNI"vj pj"jck"rj亥p."ejw鰻k"g"v瑛"PJ2-E18院p"T561-EQQJ."x "ejw鰻k" "v瑛"PJ2- V562 8院p"P791-COOH. Trên ejw鰻k" "e„"vtwpi"v¤o"z¿e"vƒe"e栄c"rncuokp"i欝o"Jku603, Asp646 và Ser741 [27]0"Ej泳e"p<pi"ukpj"j丑e"e栄c"o厩k"x́pi"p‒w"8«"8逢嬰e"n逢w"v¤o"x "zƒe" 8鵜pj0"Uqpi"uqpi"x噂k"jq衣v"v pj"e栄c"x́pi"ugtkpg"rtqvgcug."jq衣v"v pj"nk‒p"m院v"e栄c"o厩k" x́pi"M"x噂k"d隠"o員v"e栄c"eƒe"nq衣k"v院"d q"d·pj"vj逢運pi"jq員e"wpi"vj逢"8«"8逢嬰e"v·o"jk吋w." AP(E1-K77) K1(K1-E164) K2(E165-T244) K3(T245-A347) K4(P348-D461) K5(C462-A542) CL(A543-R582) SP(V562-N791) ANGIOSTATIN PL A S M IN OG E N PLASMIN
31 zƒe"okpj."8員e"dk羽v"mjk"e„"u詠"vjco"ikc"e栄c"eƒe"rj¤p"v穎"jq衣v"j„c"ej泳e"p<pi"*vRC"x " uPA). Vtqpi"8k隠w"vt鵜"pj欝k"oƒw"e挨"vko *o{qectfkcn"kphctevkqp."3;:3+."8k隠w"vt鵜"pij胤p"v pj" o衣ej"vj壱p"fq"jw{院v"mj嘘k"ucw"ijfir"vj壱p."vRC"8«"8逢嬰e"u穎"f映pi"e„"jk羽w"sw違"ecq."n o" vcp"jw{院v"mj嘘k."vj»pi"o衣ej0"V瑛"3;:6"vRC"vƒk"v鰻"j嬰r"*tvRC+"8«"8逢嬰e"u穎"f映pi"8k隠w"vt鵜" pj欝k"oƒw"e挨"vko"e医r"v pj."tvRC"vtqpi"8k隠wvt鵜"n o"vcp"jw{院v"mj嘘k. Jq衣v"8瓜pi"vj栄{"rj¤p" hkdtkpqigp"j亥w"pj逢"mj»pi"8逢嬰e"pj壱p"vj医{"荏"8c"u嘘"eƒe"d羽pj"pj¤p"8k隠w"vt鵜.
2.3.2. Tri羽u ch泳ng và bi院n ch泳ng c栄a các nhi宇o"8瓜c r逸n l映c
Tt‒p"vj院"ik噂k"e„"pjk隠w"pijk‒p"e泳w"x隠"pj„o"t逸p"p {< Vƒe"ik違"Okvvcn"D.V. và
e瓜pi"u詠"*3;;6+"pijk‒p"e泳w"荏"63"DP"d鵜"t逸p"n映e"e逸p"x噂k322'"e„"dk吋w"jk羽p"vjk吋w"pk羽w." vtqpi"8„"e„"53"vt逢運pi"j嬰r"*73,17%) dk吋w"jk羽pt嘘k"nq衣p"8»pi"oƒw [16]0"V衣k"Xk羽v"Pcọ" vƒe"ik違"Piw{宇p"A羽"x "e瓜pi"u詠"*4224+"pijk‒p"e泳w"339"DP"d鵜"t逸p"n映e"e逸p"pj壱rxk羽p"8c" mjqc"Sw違pi"Pi«k."dk吋w"jk羽p"v衣k"ej厩"là 115 BN (98,4'+"ej栄"{院w"n "8cw"pj泳ẹ"d亥o"v ọ" p嘘v"rj臼pi, d医w"jk羽w"n¤o"u pi"ej栄"{院w"n "zw医v"jw{院v"pjk隠w"p挨k"*t<pị"n嬰k."vj壱p."tiêu hóa, âm 8衣q00) x "t嘘k"nq衣p"e挨"ej院"8»pi"oƒw0"Vjgq"vƒe"ik違"Piw{宇p"Mko"U挨p"x "e瓜pi" u詠"*4225+"pijk‒p"e泳w"62"DP"d鵜"t逸p"n映e"e逸p"8k隠w"vt鵜"v衣k"vtwpi"v¤o"ej嘘pi"8瓜eDX"D衣ej" Ock"ejq"vj医{"322'"8cw"u逢pi"p隠"v衣k"ej厩.":2'"e„"ej違{"oƒw"v衣k"x鵜"vt "e逸p."78.9'"e„" zw医v"jw{院vpjk隠w"p挨k0P丑e"t逸p"n映e"i¤{"v鰻p"vj逢挨pi"v衣k"ej厩"vtqpi"x”pi"37"rj¿v"jq員e"ucw" x k" ik運" pj逢" 8cw" dw嘘v." u逢pi" p隠." ej違{" oƒw." jq衣k" v穎." d亥o" oƒw." u逢pi" j衣ej" d衣ej" jw{院vÈp„"e„"vj吋"i¤{"v鰻p"vj逢挨pi"ncp"v臼c"zwpi"swcpj"x "vq p"vj¤p."t嘘k"nq衣p"swƒ"vt·pj" 8»pi"oƒw"dk吋w"jk羽p"v瑛"pj姻"8院p"p員pi"x "DP"e„"vj吋"ej院v"fq"oƒw"ej違{"mj逸r"p挨k."zw医v" jw{院v"p«q [26]. Vtk羽w"ej泳pi"e„"vj吋"zw医v"jk羽p"pic{"ucw"mjk"d鵜"t逸p"e逸p"52-82"rj¿v."8cw" u逢pi"p隠"p挨k"d鵜"e逸p"x "zwpi"swcpj"e„"vj吋"vj医{"t x k"ik運"8亥w"x "e pi"n "f医w"jk羽w" vj逢運pi"i員r"ejk院o"v噂k";2'"eƒe"vt逢運pi"j嬰r."zw医v"jw{院v."d亥o"oƒw"e„"vj吋"zw医v"jk羽p"ucw"
3-8"ik運."j衣ej"i亥p"p挨k"d鵜"e逸p"u逢pi"8cw"n "f医w"jk羽w"u噂o"e栄c"phi宇o"p丑e"8瓜e"nq k"xkrgt.
Rtqvgcug"e„"o員v"vtqpi"uw嘘v"swƒ"vt·pj"i¤{"8瓜e"n "ej医ve„"jq衣v"v pj ukpj"j丑e"chính tác
8瓜pi"x q e違"8»pi"oƒw"x "ej嘘pi"8»pi"oƒw."nên 8逢嬰e"u穎"f映pi"pj逢"o瓜v"e»pi"e映"8吋" ej育p"8qƒp"x "8k隠w"vt鵜0"
P丑e"t逸p"n映e"e pi"rj¤p"8q衣p fibrinogen (fibrinogenolysiự"i¤{"ik違o"vk吋w"e亥w" x "eƒe"{院w"v嘘"e„"nk‒p"swcp0"Eác enzyme e栄c"p丑e"jq衣v"8瓜pipj逢"vjtqodkp"*vjtqodkp-
32
like enzyme) và e„"vt丑pi"n逢嬰pi"rj¤p"v穎"49.000-570222"fcnvqpụ"jq衣v"jqƒ"hkdtkpqigp v衣q"thành màng n逢噂k"hkdtkp"vj泳"rjƒv0"Vtqpi"p丑e"t逸p"e pi"e„"eƒe"kqp"f逢挨pi"x»"e挨"*Pc+, Ca++, K+, Mg+++"o瓜v"n逢嬰pi"pj臼"mko"nq衣k"*ej·."u逸v."ocpicp."pkmgp+."ecpzk"e„"xck"vt”" jq衣v"jqƒ"rjqurjqnkrcugC40
Bσng 2.7: Rj¤p"nq衣k"eƒe"pj„o"8瓜e"v嘘"e„"vtqpi"p丑e"t逸p"n映e"gây d羽pj"n# 8»pi"oƒw"
(coagulopathy) [36] Pj„o"8瓜e"v嘘 Vƒe"8瓜pi Vk隠p"8»pi"oƒw [院w"v嘘"X"jq衣v"j„c (Va) [院w"v嘘"KZ"jq衣v"j„c (IXa) [院w"v嘘"Z"jq衣v"j„c (Xa) Jq衣v"j„c"Rtqvjtqodkp V衣q"e映e"fibrinogen Ej嘘pi"8»pi"oƒw Rtqvgkp"E"jq衣v"j„c (APC) Rtqvgkp"d医v"jq衣v"{院w"v嘘"KZ."Z 永e"ej院"vjtqodkp Phospholipase A2 Rj¤p"ik違k"hkdtkpqigp Rj¤p"ik違k"hkdtkpqigp Hq衣v"j„c plasminogen
Vƒe"8瓜pi"8院p"vj pj"o衣ej Haemorrhagins
Jq衣v"8瓜pi"vk吋w"e亥w M ej"vj ej"pi逢pi"v壱r"vk吋w"e亥w 永e"ej院"pi逢pi"v壱r"vk吋w"e亥w Jq衣v"j„c"rtqvgkp"jw{院v"v逢挨pi 泳e"ej院"UGTRKP
2.3.2. Nq衣p"p<pi oƒw"fq"t逸p"n映e"e逸p
33
p<pi" e亥o" oƒw" *jgoquvcvke" f{uhwpevkqp+." d羽pj" n#" ocq" o衣ej" *vjtqodqvke oketqcpikqrcvj{+."v鰻p"vj逢挨pi"vj壱p"e医r"v pj"*cewvg"mkfpg{"kplwt{+."8瓜v"sw鵜"fq"vjk院w"oƒw" e映e"*d瓜"荏"p«q+"*kuejgoke"uvtqmg+0
Eƒe"pijk‒p"e泳w"8«"mj鰯pi"8鵜pj"vtqpi"p丑e"t逸p"n映e"e„"eƒe"8瓜e"v嘘"i¤{"ej違{"oƒw"8„" n "ogp"vk‒w"jw益"rtqvgkp"*rtqvgcug+."vtqpi"8„"metalloprotease, serineprotease ik英"xck"vt”"
chính [18, 38]. Rtqvgcug"rjƒ"j栄{ p瓜k"o»"vj pj"o衣ej"x "i¤{"v<pi"v pj"vj医o"vj pj" o衣ej."rjƒ"x叡"e¤p"d茨pi"swƒ"vt·pj"e亥o"oƒw"d·pj"vj逢運pi"vtqpi"e挨"vj吋0"V鰻p"vj逢挨pi"p瓜k" o衣e"o衣ej"oƒw"v衣q"8k隠w"mk羽p"ejq"vk吋w"e亥w"dƒo"f pj"pi逢pi"v壱r"x "j·pj"vj pj"eƒe"{院w" v嘘"pj逢"rjqurjqnkrkf"mj荏k"8瓜pi"e挨"ej院"v衣q"jw{院v"mj嘘k (thrombogenesis)0"O員v"mjƒe" vtqpi"p丑e"e„"eƒe"protease tác 8瓜pijq衣v"j„c"eƒe"{院w"v嘘"e亥o"máu (hemostatic factors),
ej栄"{院w"n "jq衣v"jqƒ"rtqvjtqodkp"*{院w"v嘘"KK+"x "{院w"v嘘"Z."X"fq"vƒe"f映pi"vt詠e"vk院r"{院w" v嘘"KK."X0"P丑e"t逸p"n o"v鰻p"vj逢挨pi"j羽"vj嘘pi"8»pi"oƒw"x "p瓜k"o»"x "ik違k"rj„pi"tc"eƒe" ej医v"pj逢"ugtqvqpkp"v衣q"mjw{pj"j逢噂pi"e違o"泳pi"x噂k"p丑e"i¤{"eq"o衣ej0"O瓜v"nq衣v"eƒe"vƒe" 8瓜pi"p {"e„"vj吋"i¤{"8»pi"oƒw."j·pj"vj pj"e映e"jw{院v"mj嘘k"vtqpi"n”pi"o衣ej."i¤{"ik違o" vk吋w"e亥w0
O員v"mjƒe"vtqpi"p丑e"t逸p"n映e"e pi"e„"eƒe"rtqvgkp"ej嘘pi"8»pi"oƒw"vƒe"8瓜pi"n‒p" e挨"ej院"8»pi"oƒw."eƒe"rtqvgkp"p {"nk‒p"m院v"x噂k"eƒe"{院w"v嘘"KZ."Z."n o"v<pi"vk‒w"vj映"eƒe" {院w"v嘘"KZ."Z."XKK."v衣q"vj pj"ejw厩k"peptides0"Fq"8„"n o"vjk院w"j映v"Zc."vjk院w"j映v"rj泳e" j嬰r"rtqvjtqodkpcug [13].
D‒p"e衣pj"8„"p丑e"t逸p"n映e"e pi"i¤{"vk‒w"hkdtkpqigp"eƒe"gp¦{og"jq衣v"8瓜pipj逢"
thrombin (thrombin-like enzyme) làm vk‒w"vj映"hkdtkpqigp [21, 42]0"A欝pi"vj運k"eƒe"{院w" v嘘"jq衣v"j„c"pjcpj"ej„pi"rncuokpqigp vj pj"rncuokp"vƒe"8瓜pi"n‒p"o pi n逢噂k"hkdtkp" f磯p"8院p"vk‒w"hkdtkp"o瓜v"eƒej"pjcpj"ej„pi"i¤{"zw"j逢噂pi"zw医v"jw{院v, e„"vj吋"fk宇p"tc" u噂o"vtqpi"x”pi"52"rj¿v"x "e„"vj吋 kéo dài 12-3:"ik運0"P丑e"t逸p"n映e"e”p"e„"ej医v"vjw益"
phân casein, ester arginin, axit arginylglycylcurctvke"vt丑pi"n逢嬰pi"rj¤p"v穎"vj医r"e„"jq衣v" v pj"泳e"ej院"pi逢pi"v壱r"vk吋w"e亥w."jq衣v"jqƒ"rtqvgkp"E"n o"vjqƒk"j„c {院w"v嘘 Va và VIIIa
f磯p"8院p"vk‒w"vj映"fibrinogen [31].
Pj逢"x壱{."nq衣p"p<pi"e亥o"oƒwfq"p丑e"t逸p"n映e"n "fq"vk‒w"vj映"jq員e"泳e"ej院"eƒe"{院w" v嘘"8»pi"oƒw"i¤{"zw医v"jw{院v."DP"t挨k"x q"v·pj"vt衣pi"8»pi"oƒw"p瓜k"o衣ej"t違k"tƒe"*FKE+." o瓜v"o員v"v衣q"tc"eƒe"rj¤p"8q衣p"hkdtkp."n o"zw医v"jk羽p"eƒe"jw{院v"mj嘘k"pj臼"t違k"tƒe"vtqpi" n”pi"o衣ej."8欝pi"vj運k"swƒ"vt·pj"vk‒w"hkdtkp"f磯p"8院p"vk‒w"vj映"swƒ"pjk隠w"eƒe"{院w"v嘘"8»pi"
34
oƒw"x "j壱w"sw違"n "vjk院w"oƒw"v鰻"ej泳e"i¤{"vjk院w»z{"v鰻"ej泳e"x "zw医v"jw{院v"*eƒe"d逢噂e" e挨"d違p"e栄c"swƒ"vt·pj"e亥o"oƒw"8逢嬰evt·pj"d {"荏rj映"n映e"KK+.
V„o"nＴk."eƒe"nq k"tｈp"vjwじe"jが"tｈp"nつe"*xkrgtkfcg+"i¤{"8じe"jう"jw{ｘv"oＴej"
(hemotoxic)."8ｐe"dkうv"n "tｈp"nつe"8w»k"8ぎ0"Eƒe"rj¤p"vぬ"i¤{"8じe"ej pj"vtqpi"pがe"n " pjのpi"rtqvgkpe„"jqＴv"v pj"proteasẹEƒe"rtqvgcug"pがe"tｈp"8⇔c"x q"e￢"vjあ"piq k"rjƒ" jて{"eƒe"o»"vＴk"ejざ"e”p"e„"vjあ"jqＴv"j„c"eƒe"vkｚp"rtqvgcug"*¦{oqigp+"eてc"o»"jqｐe"pｘw" x q" oƒw" vwＺp" jq p" ej¿pi" jqＴv" j„c" eƒe" vkｚp" rvqvgcug" eてc" jう" eＺo" oƒw0"Do các protease eてc"pがe"e„"vjあ"vƒe"8じpị"i¤{"tぐk"nqＴp"x q"eƒe"jう"vjぐpi"gp¦{og"dＶq"8Ｖo"uば" pじk"jｊpi"8おpj"ukpj"n#"*jqogquvcukự"jqＴv"j„c"eƒe"gp¦{og pじk"ukpj"eƒej"dＸv"vj⇔ぜpị" i¤{"jｆw"swＶ"dうpj"n#"vtＺo"vtがpị"p‒p"e￢"ejｘ"i¤{"8じe"8⇔ぢe"vt·pj"d {"swc"jう"vjぐpi" jw{ｘv"oＴej."8»pi"eＺo"oƒw."jう"vjぐpi"rtqvgcug"ぞ"eƒe"o»"nk‒p"mｘv."vtw{ｚp"v p"jkうw"swc" o pi"vｘ"d q0"J￢p"pのc."vtqpi"pがe"tｈp"nつe"8w»k"8ぎ"ejとc"pjkｚw"rtqvgkp"iげo"ugtkpg" rtqvgcug"x "ogvcnnq"rtqvgcug"e„"vƒe"8じpi"x q"jう"eＺo"oƒw0"D‒p"eＴpj"8„."gp¦{og"vjco" ikc"vtqpi"xkうe"8»pi"oƒw"e pi"n "ugtkpg"rtqvgcug."eƒe"gp¦{og"p {"vwＺp"jq p"vtqpg
oƒw"ぞ"fＴpi"vkｚp"gp¦{og"*¦{oqigp+"ej⇔c"jqＴv"8じpi"x "ejえ"jqＴv"j„c"mjk"oＴej"oƒw"dお" vごp"vj⇔￢pị"jqＴv"j„c"n o"¦{oqigp"oＸv"oじv"8qＴp"rgrvkfg0"X·"xｆ{."áp fつpi mぶ"vjwｆv" rj¤p"v ej"x "vkｘp"j pj"vj "pijkうo"8あ"n o"t "xＸp"8ｚ"vt‒p"vjばe"jkうp"ぞ"ej⇔￢pi"mｘ"vkｘr<" xｆv"nkうw"x "rj⇔￢pi"rjƒr0"
35
EJ姶愛PI"5< X一V"NK烏W"XÉ"RJ姶愛PI"RJèR
3.1. VJ云K"IKCP"XÉ"A卯C"AK韻OVK蔭P"JÉPJ"VJë"PIJK烏O
Vj運k"ikcp"vk院p"hành: v瑛"2312814235"8院p"5312714236
A隠"v k"8逢嬰e"vj詠e"jk羽p"v衣k"rj”pi"J„c"Ok宇p"F鵜ej-Xk羽p"Rcuvgwt"Vj pj"rj嘘"J欝"
Chí Minh.
Vk院p"vt·pj"vj "pijk羽o"8逢嬰e"ejkc"n o"5"ikck"8q衣p<
Ikck"8q衣p"3: Ár"f映pi"m悦"vjw壱v"zƒe"8鵜pj"vj pj"rj亥p"i¤{"8瓜e"x "jq衣v"v pj"ukpj" j丑e"e栄c"P丑e"t逸p"n映e"8w»k"8臼 (Trimeresurus albolabris).
Ikck"8q衣p"4: Ár"f映pi"eƒe"m悦"vjw壱v"vkpj"u衣ej"ugtkpg"rtqvgcug"v瑛"p丑e"t逸p"n映e"8w»k" 8臼0"Zƒe"8鵜pj"nk隠wv鰻p"vj逢挨pi"8逢運pi"m pj"32"oo"x́pi"f逢噂k"fc"ejw瓜v"*OJF+0 Ikck"8q衣p"5<"Vj穎"pijk羽o"vtwpi"j”c"p丑e"t逸p"n映e"và kháng huy院v"thanh kháng
p丑e"8吋"zƒe"8鵜pj"m院v"sw違n{"ik違k"oƒw"x́pi"f逢噂k"fc"ejw瓜v.
M院v"sw違"vj詠e"pijk羽o"e栄c"ikck"8q衣p"3"n "x壱vnk羽w"vj詠e"j pj"e栄c"ikck"8q衣p"40M院v" sw違"e栄c"ikck"8q衣p"4"n "x壱v"nk羽w"vj詠e"j pj"e栄c"ikck"8q衣p"50
3.2. X一V"NK烏W"
3.2.1. A嘘k"v逢嬰ng nghiên c泳u
‚ P丑e"Trimeresurus albolabris 8逢嬰e" Vtwpi" v¤o" Pw»k" vt欝pi" x " ej院" dk院p" F逢嬰e"nk羽w"SM";."Vk隠p"Ikcpi"ewpi"e医r"荏"f衣pi"mj»="p丑e"8逢嬰e"vjw"vj壱r"v瑛" pjk隠w"t逸p"pw»k"vtqpi"8k隠w"mk羽p"dƒp"v詠"pjk‒p"e栄c"Vt衣k"t逸p"A欝pi"V¤o0
‚ Ejw瓜v"pj逸v"Uykuu"vj "pijk羽o"8院p"v瑛"Rj”pi"ej<p"pw»k"u¿e"x壱v"vj "pijk羽o" e栄c"xk羽p"Rcuvgwt"ewpi"e医r"*vt丑pi"n逢嬰pi"v瑛"3:-20 g).
3.2.2. Thi院t b鵜
‚ J羽" vj嘘pi" u逸e" m#" v詠" 8瓜pi" ʻMVCgzrnqtgtTM 100 Air, Amersham-GE Healthcarẹ
‚ J羽"vj嘘pi"oƒ{"8丑e"GLISA, Thermọ
‚ Oƒ{"swcpi"rj鰻"WX-Vis U3310, Hitachi
36
‚ Oƒ{"8k羽pfk"ÐUPGYÑ0
‚ Oƒ{"8q"rJ"OR"442"*Ogvvngt"Vqngfq+"
‚ E¤p"rj¤p"v ej"26"u嘘"n飲<"CD-204S (Mettler Toledo).
‚ Máy vortex, IKẠ
‚ D吋"栄"pjk羽v0
3.2.3. Hóa ch医t
‚ Sepharose 6B-Dgp¦cokfkpg"*IG"Jgcnvjectg."Vj映{"Ak吋p+ ‚ DEAE Sepharose CL 6B *IG"Jgcnvjectg."Vj映{"Ak吋p+ ‚ Agarose (FMC, O悦+."o w"Rqpegcw"U0
‚ Acrylamide; N-PÓ-methylene-bis-cet{ncokfg."fwpi"f鵜ch Bradford 4X.
‚ Hw{院v"vjcpj"mjƒpi"p丑e"t逸p"n映e"*Xk羽p"X逸e"zkp"Pjc"Vtcpi+.
‚ V医v"e違"j„c"ej医v"x "8羽o"fwpi"vtqpi"vj "pijk羽o"8隠w"8衣v"{‒w"e亥w"rj¤p"
37
3.3. RJ姶愛PI"RJèR
3.3.1. U挨"8欝 n瓜i dung th詠c hi羽p"8隠 tài
3.3.2. Chu育n b鵜 dung d鵜ch n丑c r逸n l映c
+ Rjc"p丑e"t逸p"n映e"vtqpi"RDU"3Z."NaN3 0,05%: 5 mg/mL. Cân 75 oi"p丑e" t逸p."j”c"vcp"vtqpi"35 on"8羽o"RDU"3Z."NaN3 0,05%. N逸e 8隠w cho 8院p"
38 + N{"v¤o"fwpi"f鵜ej"p丑e"x噂k"x壱p"v嘘e 5222"x”pi1rj¿v"vtqpi"37"rj¿v"v衣k" 40C0"Vjw"fwpi"f鵜ej"p鰻k0 + Zƒe"8鵜pj"p欝pi"8瓜"rtqvgkp"vtqpi"fwpi"f鵜ej"d茨pi"rj逢挨pi"rjƒr"o壱v"8瓜" swcpi"荏"d逢噂e"u„pi"4:2"po0" 3.3.3. Rj逢挨pi"rjƒr"8鵜pj"n逢嬰ng protein P欝pi"8瓜"rtqvgkp"8逢嬰e"zƒe"8鵜pj"swc"jck"rj逢挨pi"rjƒr"j„c"n#"8瓜e"n壱r"xà
8嘘k" ejk院w" m院v" sw違" *8吋" nq衣k" vt瑛" pj英pi" m院v" sw違" 違q+<" j医r" vj映" swcpi" 荏" 4:2po"
(A280nm+"x "f́pi"rj逢挨pi"rjƒr"Dtcfhqtf"x噂k"o w"Eqqocuukg"UGTXC"Po 35050 *v逢挨pi"8逢挨pi"e栄c"Eqoocuukg"I-250). Rj逢挨pi"rjƒr"Dtcfhqtff詠c"x q"u詠"nk‒p"m院v"e栄c"vjw嘘e"pjw瓜o"Eqqocuukxg" Dnwg"I472"x q"rtqvgkp0"Vjw嘘e"pjw瓜o"荏"f衣pi"v詠"fq"e„"vj吋"v欝p"v衣k"荏"dc"f衣pi" kqp"mjƒe"pjcw"v逢挨pi"泳pi"x噂k"eƒe"rMc"n "3.37="3.:4"x "34.60"E„"dc"f衣pi"kqp" ej栄"{院w"e栄c"ej医v"o w"v欝p"v衣k"vtqpi"fwpi"f鵜ej"rj違p"泳pi"荏"rJ"czkv."f衣pi"o w" 8臼."o w"zcpj"nƒ"e¤{"*ocpi"8k羽p"v ej"f逢挨pi+"x "o w"zcpj"n映e"*ocpi"8k羽p"v ej" ¤ơ"e„"8瓜"j医r"vjw"e詠e"8衣k"v逢挨pi"泳pi"v衣k"692."872"x "7;7"po0"Vtqpi"8k隠w"mk羽p" rJ"czkv"o衣pj."ej医v"o w"ej栄"{院w"v欝p"v衣k"f逢噂k"f衣pi"o w"8臼"*nk‒p"m院v"x噂k"4"rj¤p" v穎"J+) và khi lk‒p"m院v"x噂k"rtqvgkp"p„"v欝p"v衣k"荏"f衣pi"mj»pi"e„"rtqvqp"j„c"*o w" n映e+0"X·"x壱{."n逢嬰pi"rtqvgkp"e„"vj吋"8逢嬰e"8鵜pj"n逢嬰pi"d茨pi"eƒej"zƒe"8鵜pj"n逢嬰pi" vjw嘘e"pjw瓜o"荏"f衣pi"kqp"zcpj"n映e0"Ak隠w"p {"vj逢運pi"8逢嬰e"vj詠e"jk羽p"d茨pi"eƒej" 8q"8瓜"j医r"vj映"e栄c"fwpi"f鵜ej"荏"d逢噂e"u„pi"7;7 nm. Vjw嘘e"pjw瓜o"nk‒p"m院v"o瓜v"eƒej"pjcpj"ej„pi"x q"eƒe"pj„o"ctikpkp"x " n{ukp"jk羽p"fk羽p"vt‒p"rj¤p"v穎"rtqvgkp0"V pj"8員e"jk羽w"p {"f磯p"8院p"u詠"8c"f衣pi" vtqpi"8鵜pj"n逢嬰pi"eƒe"nq衣k"rtqvgkp"mjƒe"pjcw0"M院v"sw違"8鵜pj"n逢嬰pi"rtqvgkp"x噂k" rj逢挨pi"rjƒr"Dtcfhqtf"n "v逢挨pi"8嘘k"x噂k"ejw育p"u穎"f映pi0
Vj詠e"jk羽p<
- Fwpi"f鵜ej"albumin jw{院v"vjcpj"bò ejw育p (BSA)<"rjc"vtqpi"8羽o"RDU" *f違k"p欝pi"8瓜"8k"v瑛"2"Î 32 og/ml).
- Fwpi" f鵜ej"BSA ejw育p" x " fwpi" f鵜ej" p丑e 8逢嬰e" 栄" x噂k" fwpi" f鵜ej" Dtcfhqtf"vtqpi"7"rj¿v"v衣k"pjk羽v"8瓜"rj”pi0""
39
- J医r"rj映"swcpi"e栄c"eƒe"fwpi"f鵜ej"8逢嬰e"8q"v衣k"d逢噂e"u„pi"7;7"po0"
- F詠pi"8逢運pi"ejw育p"f詠c"vt‒p"n逢嬰pi"BSA ejw育p"x "8瓜"j医r"vj映"e栄c"p„0"
- F詠c"vt‒p"8逢運pi"ejw育p"zƒe"8鵜pj"p欝pi"8瓜"e栄c"fwpi"f鵜ej"p丑eej逢c"dk院v0
- F́pi"rj亥p"o隠o"ME6"8吋"v pj"j o"n逢嬰pi"protein có trong o磯w0
3.3.4. Rj逢挨pi"rjƒr"u逸c ký ái l詠c dùng Bezamidine Sepharose 6B 8吋 tinh ch院 serine protease trong n丑c r逸n l映c
Benzamidine SepharoseTM là p-cokpqdgp¦cokfkpg" e瓜pi" j„c" vt鵜" x噂k" Ugrjctqug" 8D" d茨pi" rj逢挨pi" rjƒr" e瓜pi" j嬰r" vj»pi" swc" pj„o" grqz{" *o瓜v" piw{‒p"v穎"qz{"nk‒p"m院v"x噂k"jck"piw{‒p"v穎"ectdqp+<"r- aminobenzamidine (PAB)
n " ej医v" 泳e" ej院" vt{rukp" nk‒p" m院v" e衣pj" vtcpj" x噂k" e挨" ej医v" 8員e" jk羽w" e栄c" ugtkpg" rtqvgcug"8吋"v衣q"rj泳e"j嬰r"GU"fq"8„"ugtkpg"rtqvgcug"8逢嬰e"i逸p"x q"e瓜v"*e„"p欝pi" 8瓜"PAB cao)0"Ucw"8„."8育{"Ugtkpg"Rtqvgcug"tc"mj臼k"e瓜v"d茨pi"fwpi"f鵜ej"8羽o"e„"
tính pH vj医r"mj»pi"rj́"j嬰r"ejq"jq衣v"8瓜pi"v衣q"GU0"T穎c"e瓜v"x "d違q"sw違p"荏"6OC [5, 10, 33].
Vj詠e"jk羽p<"
Ejq"33"oN"p丑e"swc"e瓜v"Dg¦cokfkpg"Ugrjctqug"8D0"T穎c"e瓜v"d茨pi"fwpi" f鵜ej"8羽o"Tris-JEn"42"oỌ"PcEn"2.7"Ọ"rJ?9.6"ejq"8院p"mjk"f鵜ej"t穎c"mj»pi"
còn protein (OD280?2+0"A育{"vj pj"rj亥p"dƒo"vt‒p"e瓜v"fwpi"f鵜ej"in{ekpg"72oỌ" rJ?502"*8院p"mjk"f鵜ej"tc"có OD280=0), ejq"x q"嘘pi"j泳pi"8q衣p"e„ Tris 1 M,
rJ?:0"Vjw"gp¦{og"vkpj"ej院0"E¤p"d茨pi"e瓜v"x噂k"fwpi"f鵜ej"Vtku-HCl 10 mM, NaCl 0,5 M, rJ?9.70"D違q"sw違p"e瓜v"荏"60E"8吋"u穎"f映pi"ejq"eƒe"n亥p"vkpj"ej院"ucw
[8, 10].
3.3.5. Rj逢挨pi" rjƒr" 8k羽p" fk" vt‒p" vj衣ej" rqn{cet{lamide 12% x噂k" Uqfkwo" dodecylsulfate (SDS-PAGE)
Ak羽p"fk"n "rj逢挨pi"rjƒr"rj¤p"vƒej"f詠c"x q"u詠"ejw{吋p"8瓜pi"e栄c"eƒe"rj¤p" v穎"v ej"8k羽p"vtqpi"x́pi"8k羽p"vt逢運pi0"Rtqvgkp"荏"f衣pi"vk吋w"8挨p"x鵜"ucw"mjk"eƒe"nk‒p" m院v"ÎS-S- 8«"d鵜"e逸v"*mj穎"x噂k"fkvjkqvjtgkvqn."UFỤ";7oC, 7"rj¿v+"8逢嬰e"ejq"rj泳e" j嬰r"x噂k"UFU="f衣pi"rj泳e"j嬰r"dãq"j”c"x噂k"UFU"8k"swc"vj衣ej"rqn{cet{ncokfg" v́{"vjw瓜e"x q"vt丑pi"n逢嬰pi"rj¤p"v穎"e栄c"vk吋w"8挨p"x鵜"rtqvgkp1"rqn{rgrvkfg="v医v"e違"
40
eƒe"rj泳e"j嬰r"rtqvgkp"ÎUFU"8隠w"ocpi"v pj"8k羽p"¤ọ"vt丑pi"n逢嬰pi"rj¤p"v穎"càng cao càng pjk隠w"UFUnk‒p"m院v0
Các protein fk"vtqpi"o»k"vt逢運pi"vj衣ej"nk‒p"v映ẹ"mj»pi"tc"mj臼k"vj衣ej0"A吋" u詠" rj¤p" ik違k" 8逢嬰e" ecq." o壱v" 8瓜" n逢噂k" rqn{cet{ncokfg" 8逢嬰e" v<pi" n‒p" f亥p" *itcfkgpv+."v瑛"v瑛"p¤pi" ecq"8瓜" oc" uƒv"e栄c"eƒe"rj¤p"v穎"n噂p"vtqpi"n¿e"8„"eƒe" rgrvkfgu"pj臼"8k"vt逢噂e0
A嘘k" x噂k" eƒe" ugtkpg" rtqvgcug." ogvcnq" rtqvgcug p丑e" t逸p." o壱v" 8瓜" rqn{cet{ncokfg" u穎" f映pi" u胤" v<pi" v瑛" 9'" 8院p" 34" '" p欝pi" 8瓜" v鰻pi" n逢嬰pi cet{ncokfg0" M悦" vjw壱v" p {" u胤" 8逢嬰e" u穎" f映pi" 8吋" mk吋o" vtc" pj英pi" vj pj" rj亥p" rtqvgkp"jk羽p"fk羽p"vtqpi"o厩k"rj¤p"8q衣p"vƒej"8逢嬰e"swc"rj逢挨pi"rjƒr"u逸e"m#"ƒk" n詠e0 SDS-RCIG"ejq"rjfir"x瑛c"pj壱p"vj泳e"8逢嬰e"x隠"vt丑pi"n逢嬰pi"rj¤p"v穎."x瑛c" mk吋o"vtc"8瓜"vkpj"u衣ej"e栄c"eƒe"vj pj"rj亥p"vjw"j欝k"vtqpi"eƒe"rj¤p"8q衣p0"Rtqvgkp" vt‒p"vj衣ej"rqn{cet{ncokfg"8逢嬰e"pjw瓜o"x噂k"Eqqocuukxg"T-250 [30]. + - A B tå e詠e A B + - rj¤p"ik違k