Nghiên cứu ảnh hưởng của cap toàn phần và một số chất phân lập từ thân cây chuối tiêu lên sự phosphoryl hóa AMPK và IRS 1 in vitro

B Y T TRNG I HC DC H NI PHM TH THU HUYN 1201261 NGHIấN CU NH HNG CA CAO TON PHN V MT S CHT PHN LP T THN CHUI TIấU LấN S PHOSPHORYL HểA AMPK V IRS-1 IN VITRO KHểA LUN TT NGHIP DC S H NI - 2017 B Y T TRNG I HC DC H NI PHM TH THU HUYN 1201261 NGHIấN CU NH HNG CA CAO TON PHN V MT S CHT PHN LP T THN CHUI TIấU LấN S PHOSPHORYL HểA AMPK V IRS-1 IN VITRO KHểA LUN TT NGHIP DC S Ngi hng dn: PGS.TS Phựng Thanh Hng TS Th Nguyt Qu Ni thc hin: B mụn Dc Lc Trng i hc Dc H Ni H NI - 2017 LI CM N Trc tiờn, em xin gi li cm n chõn thnh cựng s tri õn sõu sc ti ton th thy cụ giỏo v cỏc anh ch k thut viờn b mụn Húa Sinh v Dc Lớ Trng i hc Dc H Ni, ó to iu kin thun li cho em quỏ trỡnh thc hin khúa lun tt nghip Vi tm lũng bit n sõu sc nht, em xin gi li cm n n PGS TS Phựng Thanh Hng - ngi thy tõm huyt ó tn tỡnh giỳp em t nhng ngy u lm khoa hc Nh nhng nh hng sỏng sut v kp thi ca cụ m bn thõn em ó la chn c nhng hng nghiờn cu ỳng n v phự hp Khụng nhng vy, cụ luụn theo sỏt em sut quỏ trỡnh lm khoa hc v kp thi a nhng li khuyờn, li ng viờn b ớch Bi hc cụ dy cho em khụng ch l kin thc chuyờn mụn, m hn c ú cũn l nhng bi hc v k nng sng T nhng bi hc v lũng quý giỏ ny, bn thõn em ó trng thnh v t tin hn ng lm nghiờn cu Em xin gi li cm n chõn thnh n TS Th Nguyt Qu - ngi thy th hai quỏ trỡnh lm khoa hc ca em c lm vic cựng cụ l mt s may mn vụ cựng ln Cụ khụng nhng ó h tr v ch dy ht mỡnh cho em nhng phng phỏp, k thut quỏ trỡnh thc hin khúa lun tt nghip, m bờn cnh ú, cụ cũn khụng ngng trau di thờm cho em nhng kin thc v k thut khoa hc mi, t ú lm giu thờm kinh nghim nghiờn cu cho bn thõn em T cụ, em ó hc c rt nhiu bi hc b ớch v s sỏng to v nim am mờ vi khoa hc Em xin gi li cm n chõn thnh ti cụ NCS Ths Nguyn Th ụng ó luụn nhit tỡnh h tr em quỏ trỡnh hc v nghiờn cu Cui cựng, em xin gi li cm n ti nhng ngi thõn gia ỡnh cựng bn bố ó luụn ng viờn v giỳp em hon thnh tt khúa lun tt nghip Em xin chõn thnh cm n! MC LC LI CM N MC LC DANH MC CC CH, Kí HIU VIT TT DANH MC CC BNG DANH MC CC HèNH T VN .1 CHNG 1: TNG QUAN .3 1.1 AMPK .3 1.1.1 Khỏi nim 1.1.2 Cu trỳc 1.1.3 Vai trũ ca protein AMPK t bo 1.1.4 Vai trũ ca protein AMPK iu tr ỏi thỏo ng 1.1.5 Cỏc nghiờn cu v tỏc dng hot húa protein AMPK .8 1.2 IRS-1 .10 1.2.1 Khỏi nim .10 1.2.2 Cu trỳc 10 1.2.3 Vai trũ ca protein IRS-1 t bo 11 1.2.4 Vai trũ ca s phosphoryl húa IRS-1 iu tr ỏi thỏo ng .14 1.2.5 Cỏc nghiờn cu v tỏc dng c ch s phosphoryl húa Ser307 trờn IRS-1 15 1.3 Cõy chui tiờu (Musa paradisiaca L - Musaceae) 16 1.3.1 V trớ, phõn loi 16 1.3.2 c im thc vt v phõn b 16 1.3.3 B phn dựng 17 1.3.4 Cỏc nghiờn cu v tỏc dng gõy h glucose mỏu ca thõn cõy Chui tiờu 18 CHNG 2: I TNG V PHNG PHP NGHIấN CU 19 2.1 i tng nghiờn cu .19 2.1.1 Nguyờn liu nghiờn cu 19 2.1.2 T bo thớ nghim 19 2.1.3 Thit b, dng c, hoỏ cht nghiờn cu 19 2.2 Ni dung nghiờn cu 21 2.3 Phng phỏp nghiờn cu 21 2.3.1 Phng phỏp ỏnh giỏ nh hng ca mu nghiờn cu lờn s phosphoryl húa AMPK v IRS-1 22 2.3.2 Phng phỏp x lớ s liu 27 CHNG 3: KT QU 28 3.1 nh hng trờn s phosphoryl húa AMPK (Thr172) ca cao ton phn v mt s cht phõn lp t dch ộp thõn cõy Chui tiờu .28 3.1.1 nh hng trờn s phosphoryl húa AMPK (Thr172) ca cao ton phn 28 3.1.2 nh hng trờn s phosphoryl húa AMPK (Thr172) ca hai cht phõn lp t dch ộp thõn cõy chui tiờu 29 3.2 nh hng trờn s phosphoryl húa IRS1 (Ser307) ca cao ton phn v hai cht phõn lp t dch ộp thõn cõy chui tiờu 31 3.2.1 nh hng trờn s phosphoryl húa IRS1 (Ser307) ca cao ton phn 31 3.2.2 Tỏc dng c ch s phosphoryl húa IRS1(Ser307) ca hai cht phõn lp t dch ộp thõn cõy chui tiờu 33 CHNG 4: BN LUN 35 4.1 V phng phỏp nghiờn cu 35 4.2 V nh hng ca cỏc mu th trờn s phosphoryl húa AMPK 35 4.3 V nh hng trờn s phosphoryl húa IRS1 37 KT LUN .40 KIN NGH 40 TI LIU THAM KHO PH LC DANH MC CC CH, Kí HIU VIT TT ACC Acetyl-CoA carboxylase ACC1/ACC2 Acetyl-CoA carboxylase 1/2 ADP Adenosine diphosphat AICAR 5-aminoimidazole-4-carboxamide riboside AIS Auto-inhibitory sequence Akt/PKB Protein kinase B AMPK 5'-adenosine monophosphate-activated protein kinase AS160 AKT substrate of 160 kDa ATP Adenosine triphosphat BAD Bcl-2-associated death promoter CaMK-K Calmodulin-dependent protein kinase kinase CBD Carbohydrate-binding module CPT1 Carnitineacylcarnitine translocase T ỏi thỏo ng eNOS Endothelial nitrogen oxyd synthetase ERK Extracellular signal-regulated kinase FA Fatty acid (acid bộo) GBD Glycogen-binding domain GLUT4 Glucose transporter Grb-2/Sos Growth factor receptor-bound protein 2/son of sevenless GSK3 Glycogen synthase kinase HDAC Histone deacetylase HMG-CoA reductase 3-hydroxy-3-methyl-glutaryl-CoA reductase IGF-1 Insulin-like growth factor-1 IR Insulin receptor IRS-1 Insulin receptor substrate-1 LKB1 Liver kinase B1 MAPK Mitogen-activated protein kinase MCD Malonyl-CoA decarboxylase mtGPAT Mitochondrial sn-glycerol-3-phosphate acyltransferase mTOR Mammalian target of rapamycin Nck Non-catalytic region of tyrosine kinase PGC-1 Peroxisome proliferator-activated receptor gamma coactivator-1 alpha PH Pleckstrin-homology PI3K/PDK1 Phosphatidylinositide 3-kinase PKC Protein kinase C PTB Phosphotyrosine-binding Ptd(3,4,5)P3 Phosphatidylinositol (3,4,5) triphosphat PtdIns(4,5)P2] Phosphatidylinositol (4,5) bisphosphat PTP1B Protein-tyrosine phosphatase 1B Ser Serine SH2 Src-homology-2 SID Subunit interacting domain SIRT1 Sirtuin Syp Synaptophysin TSC1/TSC2 Tuberous sclerosis complex and DANH MC CC BNG Bng 2.1 Cỏc húa cht dựng thớ nghim Trang 20 Bng 2.2 Cụng thc solution gel v sereprating gel Trang 24 Bng 2.3 La chn khỏng th theo protein ớch cn nhn bit Trang 26 DANH MC CC HèNH Hỡnh 1.1 Cu trỳc ca protein AMPK Trang Hỡnh 1.2 Con ng truyn tớn hiu ca AMPK Trang Hỡnh 1.3 Cu trỳc ca protein IRS-1 Trang 10 Hỡnh 1.4 Con ng truyn tin ni bo ca IRS-1 Trang 12 Cõy chui tiờu chp xó Giang sn, huyn Gia Bỡnh, Hỡnh 1.5 Hỡnh 2.1 S thit k nghiờn cu Hỡnh 2.2 S quy trỡnh thớ nghim ỏnh giỏ nh hng ca mu th trờn s phosphoryl húa ca p-IRS v p- Trang 22 AMPK Hỡnh 3.1 Tỏc dng ca cao ton phn cỏc nng khỏc Trang 28 trờn lng AMPK phosphoryl húa Thr172 Hỡnh 3.2 So sỏnh lng p-AMPK(Thr172) gia cỏc lụ cao Trang 29 ton phn cỏc nng khỏc 10 Hỡnh 3.3 Tỏc dng ca Cycloeucalenon (H1) v Daucosterol Trang 30 (H2) trờn lng AMPK phosphoryl húa Thr172 11 Hỡnh 3.4 So sỏnh lng p-AMPK(Thr172) gia cỏc lụ Cycloeucalenon (H1) v Daucosterol (H2) cỏc Trang 31 nng khỏc 12 Hỡnh 3.5 Tỏc dng ca cao ton phn cỏc nng khỏc Trang 32 trờn lng IRS-1 phosphoryl húa Ser307 13 Hỡnh 3.6 So sỏnh lng p-IRS-1(Ser307) gia cỏc lụ cao Trang 32 ton phn cỏc nng khỏc 14 Hỡnh 3.7 nh hng ca Cycloeucalenon (H1) v Daucosterol (H2) cỏc nng khỏc trờn lng IRS-1 Trang 33 phosphoryl húa Ser307 15 Hỡnh 3.8 So sỏnh lng p-IRS-1(Ser307) gia cỏc lụ Cycloeucalenon (H1) v Daucosterol (H2) cỏc Trang 34 nng khỏc tnh Bc Ninh (Musa paradisiaca L.) Trang 17 Trang 21 T VN ỏi thỏo ng (T) ang thc s l mi lo ngi ln i vi xó hi bi tc gia tng chúng mt hin Theo thng kờ mi nht ca Hip hi ỏi thỏo ng Quc t (IDF), nm 2015, c th gii cú 415 triu ngi mc bnh T, theo c tớnh, s ny s tng lờn thnh 642 triu ngi vo nm 2040 Ti thi im nm 2015, c 10 ngi ln li cú mt ngi b T C giõy li cú mt ngi t vong vỡ T v tng cng, cn bnh ny ó cp i mng sng ca triu ngi vũng mt nm Cựng vi nhng hu qu nghiờm trng, T ang tr thnh mt gỏnh nng ln cho ngnh Y t vi chi phớ iu tr trc tip mi nm cho bnh nhõn lờn n 673 t ụ la, chim 9-16% ngõn sỏch chm súc sc khe ca th gii [26] Mt khỏc, cỏc thuc iu tr T cú ngun gc tng hp húa hc hin thng kốm theo nhiu tỏc dng khụng mong mun, ngi bnh cú xu hng phi tng liu sau mt thi gian di dựng thuc [1] Nhm khc phc nhng im bt cp ny, xu hng Tỡm v thiờn nhiờn vi vic tỡm kim v nghiờn cu cỏc thuc mi cú ngun gc t dc liu ang ngy cng thu hỳt c nhiu s quan tõm ca Y-Dc hc hin i Cõy chui tiờu (Musa paradisiaca L.) c bit n rng rói nh mt loi thc phm v cng l mt v thuc Theo kinh nghim dõn gian ca ng bo dõn tc thiu s phớa bc Vit Nam v mt s quc gia trờn th gii, dch ộp thõn cõy chui tiờu dựng iu tr T cú tỏc dng h glucose mỏu rt tt Trờn th gii cú mt vi nghiờn cu v tỏc dng cha T ca thõn cõy chui tiờu nhng ch mi mc sng lc, kt qu cha thng nht, c bit, cha cú mt nghiờn cu cú h thng no ỏnh giỏ c tỏc dng v c ch tỏc dng h glucose mỏu ca dc liu ny [48] [53] [56] Ti Vit Nam, nm 2015, Phựng Thanh Hng v Nguyn Th ụng ó chng minh c dch ộp thõn cõy Chui tiờu cú tỏc dng h glucose mỏu trờn chut nht trng b gõy T thc nghim bi STZ vi mc liu 150mg/kg cõn nng [4] Nm 2016, Phựng Thanh Hng cựng cỏc cng s ó chng minh c tỏc dng h glucose huyt ca dch ộp thõn cõy chui tiờu thụng qua c ch c ch hot tớnh PTP1B in vitro [3] gúp phn lm phong phỳ thờm nhng bng chng i vi cht phõn lp Cycloeucalenon (H1) v Daucosterol (H2), kt qu cho thy, cú s gia tng lng p-AMPK tng nng ca mu th ging phn ng Tuy nhiờn, c nng th (25 àg/ml v 50 àg/ml) ca Cycloeucalenon (H1) v Daucosterol (H2) u khụng lm tng lng p-AMPK so vi lụ chng õm (p>0,05) Rt cú th tng thi gian thuc hoc tng nng mu th, s cú th t c s khỏc bit cú ý ngha thng kờ v s phosphoryl húa AMPK 4.3 V nh hng trờn s phosphoryl húa IRS1 IRS1 l mt sỏu c cht ca Insulin receptor (IR) [24], cựng vi nhiu protein khỏc, tham gia vo ng truyn tin ni bo ca insulin Di tỏc dng kớch thớch ca insulin, IR hot húa v tng tỏc vi IRS-1 Ngay sau ú, cỏc gc tyrosin trờn IRS-1 c phosphoryl húa v kớch hot cỏc bc tip theo chui truyn tin ni bo ca insulin, cui cựng lm gia tng nhanh chúng s dung np glucose vo t bo thụng qua vic lm gia tng s lng GLUT [52] Vỡ vy, s phosphoryl húa cỏc gc tyrosin ca IRS-1 nh hot tớnh tyrosin kinase ca IR l mt bc quyt nh chui truyn tin ni bo nhm hot húa cỏc ớch phõn t tip theo Tuy nhiờn, bờn cnh s phosphoryl húa cỏc gc tyrosin, IRS-1 cũn cú th b phosphoryl húa cỏc gc serin/threonin nhiu v trớ khỏc Nhiu nghiờn cu cho thy, s phosphoryl húa cỏc gc serin/threonin trờn IRS-1, c bit l Ser307 li gõy xut hin tỡnh trng khỏng insulin hoc T type II [47] [54] [55] Quỏ trỡnh phosphoryl húa Ser307 IRS-1 c ch protein ny liờn kt vi IR phosphoryl húa cỏc gc tyrosin [66] Lỳc ny, vựng SHP2 trờn phõn t IRS-1 khụng cũn l cỏc v trớ gn cho cỏc phõn t ni bo cha vựng SH2, bao gm PI3K v Grb-2, t ú c ch hai ng PI3K v MAPK Hu qu l lm tng tỡnh trng khỏng insulin v gim s hon thin ca t bo Vỡ vy, s phosphoryl húa Ser l c ch gõy c ch chui truyn tin ni bo ca insulin t ú phỏt trin thnh tỡnh trng T type II Theo nhiu tỏc gi, IRS-1 c coi l mt ớch tỏc dng tim nng iu tr T mang li tỏc dng tng cng nhy cm vi insulin, cú th tỏc ng lờn 37 protein ny theo nhiu xu hng khỏc Trong ú, hai xu hng chớnh c nghiờn cu nhiu nht l tng cng s phosphoryl húa cỏc gc tyrosin hoc c ch s phosphoryl húa cỏc gc serin, c bit l Ser307, trờn phõn t IRS-1 Thc t, xu hng nghiờn cu v cỏc cht cú kh nng c ch s phosphoryl húa IRS-1 (Ser307) lm gim tỡnh trng khỏng insulin mi bt u c quan tõm nhng nm gn õy Theo nghiờn cu ca Weidong Yin nm 2014, t bo to m 3T3-L1 b gõy khỏng insulin trc ú bi acid palmitic (300àM, 6h) sau c vi metalonin vũng 30 phỳt, cú s gia tng ỏng k lng GLUT-4 v gim lng IRS-1 c phosphoryl húa v trớ Ser307 [35] Nm 2015, Gyửrgy Kộri cựng cỏc cng s ó tin hnh mt nghiờn cu ln nhm sng lc kh nng c ch s phosphoryl húa Ser307 trờn IRS-1 mụ hỡnh t bo b gõy khỏng insulin thc nghim ca 51 hp cht l dn cht ca pyrido[2,3-d] pyrimidin-7-on Kt qu nghiờn cu ó ch 5/51 hp cht c ch hiu qu s phosphoryl húa Ser307 ca IRS-1 Mc dự s phosphoryl húa gc serin trờn IRS-1 cú th xy nhiu v trớ khỏc nh Ser-307, -302 v -318 [22] nhng v trớ c nghiờn cu nhiu nht l Ser307 Vỡ vy nghiờn cu ny chỳng tụi s dng khỏng th khỏng IRS-1 c phoshoryl húa v trớ Ser307 quy trỡnh Western blot Kt qu nghiờn cu cho thy i vi cao ton phn, cú s gim dn lng pIRS-1(Ser307) tng nng cao hn hp phn ng Tuy nhiờn, c nng th (12,5 àg/ml, 25 àg/ml, 50 àg/ml) u khụng lm gim lng p-IRS1(Ser307) cú ý ngha thng kờ so vi lụ chng (p > 0,05) i vi cht phõn lp Cycloeucalenon (H1) v Daucosterol (H2), nghiờn cu tip tc ỏnh giỏ kh nng c ch s phosphoryl húa IRS-1(Ser307) thụng qua lng p-IRS-1(Ser307) ti nng 25 àg/ml v 50 àg/ml Kt qu sau t bo vi cỏc mu th gi cho thy, Cycloeucalenon (H1) khụng lm thay i lng p- IRS-1(Ser307) cú ý ngha thng kờ so vi lụ chng Trong ú, Daucosterol (H2) th hin kh nng c ch s phosphoryl húa IRS-1(Ser307) lm gim lng p-IRS-1(Ser307) so vi lụ chng Tỏc dng c ch ca Daucosterol (H2) tng lờn tng nng ca 38 cht ny cỏc ging th Tuy nhiờn, ch cú nng 50 àg/ml lm gim lng p-IRS-1(Ser307) cú ý ngha thng kờ so vi lụ chng (p=0,0015) Nh vy, theo kt qu ca nghiờn cu, Cycloeucaleon khụng cú tỏc dng hot húa AMPK (Thr172), ng thi cng khụng cú tỏc dng c ch s phosphoryl húa IRS-1 (Ser 307) Cỏc tỏc dng sinh hc ca Cycloeucalenon ó c nghiờn cu trc ú bao gm: chng tiờu chy [7] [8]; gim au, chng viờm [40], iu hũa v kim soỏt nh nhp tim [40] V theo cỏc ti liu chỳng tụi tỡm hiu c, mi cú nghiờn cu ca Nguyn Th Huyn chng minh cycloeucalenon phõn lp t dch ộp thõn cõy Chui tiờu th hin tỏc dng c ch PTP1B mnh vi IC50 l 3,11àM [3] Ngc li vi Cycloeucalenon, tỏc dng h glucose mỏu ca Daucosterol ó c chng minh qua nhiu nghiờn cu Daucosterol (phõn lp t loi Urtica angustifolia) cú tỏc dng lm tng dung np glucose mỏu test dung np glucose bng ng ung trờn chut thc nghim [32] Theo nghiờn cu ca Mitsuo Miyazawa v cng s nm 2005, daucosterol chit xut t Arctium lappa L cú tỏc dng c ch 97,3% hot ng -glucosidase nng 200,0 mol/ml v ID50 l 30 mol/ml [39] Trong ti ny, Daucosterol ó c chng minh cú kh nng c ch s phosphoryl húa IRS-1(Ser307) nng 50 àg/ml ca cht ny lm gim lng p-IRS-1(Ser307) cú ý ngha thng kờ so vi lụ chng Kt qu ny gúp phn lm sỏng t thờm c ch gõy h glucose mỏu ca Daucosterol núi riờng v ca cao ton phn thõn cõy Chui tiờu núi chung bờn cnh cỏc nghiờn cu ó c cụng b trc ú 39 KT LUN i vi tỏc dng tng phosphoryl húa AMPK (Thr172), cao ton phn thõn Chui tiờu nng 50 àg/ml lm tng lng p-AMPK(Thr172) cú ý ngha thng kờ Hai cht phõn lp t thõn Chui tiờu Cycloeucalenon v Daucosterol khụng lm tng lng p-AMPK(Thr172) cú ý ngha thng kờ so vi lụ chng i vi tỏc dng c ch s phosphoryl húa IRS-1(Ser307), ti cỏc nng th nghim, cao ton phn thõn Chui tiờu khụng lm gim lng IRS-1(Ser307) cú ý ngha thng kờ so vi lụ chng i vi hai cht phõn lp t thõn cõy Chui tiờu, ch cú nng 50 àg/ml ca Daucosterol lm gim lng p-IRS-1(Ser307) cú ý ngha thng kờ so vi lụ chng KIN NGH Tip tc nghiờn cu theo hng t bo vi cao ton phn v cỏc cht phõn lp vi cỏc nng cao hn v khong thi gian di hn cú th ỏnh giỏ ton din hn v tỏc dng trờn s phosphoryl húa AMPK v IRS1 Cn cú thờm cỏc nghiờn cu tip theo v tỏc dng ca cao ton phn, cao phõn on v cỏc cht phõn lp trờn nhng protein ớch khỏc liờn quan n ng truyn tớn hiu ca insulin giỳp lm rừ hn tỏc dng v c ch tỏc dng ca dc liu ny 40 TI LIU THAM KHO TING VIT T Vn Bỡnh (2004), Nhng nguyờn lý nn tng bnh ỏi thỏo ng tng glucose mỏu, Nh xut bn Y hc, H Ni, tr 23, 26-27, 53-54, 171-249, 280, 293, 792-794 Vừ Vn Chi (2012), T in cõy thuc Vit Nam, Tp 1, Nh xut bn Y hc, H Ni, tr 467-469 Nguyn Th Huyn (2016), Nghiờn cu tỏc dng c ch PTP1B in 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hn hp ca cht thuc khung sterol, FE1.2 (20mg) v FE1.3 (400mg), FE1A (130 mg) Phõn on FE1.2 c tinh ch qua ct silica gel vi h dung mụi n-Hexan/ CH2Cl2 gradient (0-30%) thu c hp cht FE1C (9 mg) l cht du mu trng Phõn on FE4 (90 mg) c tinh ch qua ct silica gel vi h dung mụi n-Hexan/ CH2Cl2 gradient (0-30%) thu c hp cht -sistosterol (18 mg) Phõn on FE6 (0,2 g) c cho lờn ct ct Sephadex LH20 khai trin vi h dung mụi CH2Cl2/MeOH (8/2) thu c phõn on FE6.1 (100mg) v FE6.2 (60mg) Phõn on FE6.1 c tinh ch qua ct silica gel h dung mụi n-Hexan/EtOAc (5 :1) thu c cht sch FE6B (30mg) l cht rn mu trng Phõn on FE10 (0,1 g) tinh ch qua ct Sephadex LH20 khai trin vi h dung mụi CH2Cl2/MeOH (8/2) thu c hp cht sch ký hiu FE10A (28 mg) l cht rn mu trng Phõn on FE12 cng c tinh ch qua ct Sephadex LH20 khai trin vi h dung mụi CH2Cl2/MeOH (8/2) thu c cht sch FE12A (15mg) l cht rn mu trng S phõn lp phõn on Ethyl acetat Ghi chỳ: A (aceton); D (dichlomethan); H (n-hexan); M (methanol); E (ethyl acetat) Kt qu xỏc nh cu trỳc ca cỏc cht phõn lp c: STT Cn ethylacetat FE1C Tờn cht: Cycloeucalenon Cụng thc phõn t: C30H48O M=424.70152 g/mol FE10A Tờn cht: Protocatechuic acid Cụng thc phõn t: C7H6O4 M= 154.12g/mol FE6B Tờn cht: Myristic acid Cụng thc phõn t: C14H28O2 M=228.38 g/mol FE12.A Tờn cht: Daucosterol Cụng thc phõn t: C35H60O6 M=576.86 g/mol ... DƯỢC HÀ NỘI PHẠM THỊ THU HUYỀN 12 012 61 NGHIÊN CỨU ẢNH HƯỞNG CỦA CAO TOÀN PHẦN VÀ MỘT SỐ CHẤT PHÂN LẬP TỪ THÂN CHUỐI TIÊU LÊN SỰ PHOSPHORYL HÓA AMPK VÀ IRS- 1 IN VITRO KHÓA LUẬN TỐT NGHIỆP DƯỢC SĨ... cao toàn phần hai chất phân lập từ dịch ép thân chuối tiêu 31 3.2 .1 Ảnh hưởng phosphoryl hóa IRS1 (Ser307) cao toàn phần 31 3.2.2 Tác dụng ức chế phosphoryl hóa IRS1 (Ser307) hai chất phân. .. chế tác dụng thân chuối tiêu điều trị ĐTĐ, tiến hành đề tài: Nghiên cứu ảnh hưởng cao toàn phần số chất phân lập từ thân Chuối tiêu lên phosphoryl hóa AMPK IRS- 1 in vitro với mục tiêu sau: Đánh