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The Studies Of SalB And XML Treating On Heart Failure

Posted on:2018-04-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:J YuFull Text:PDF
GTID:1364330518965053Subject:Zoology
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Background:Heart failure is a dangerous disease which influences millions of patients.The Chinese medicine have great advantages on the treatment of heart failure.The present study is aimed to investigate the effect of salvianolic acid B(SalB)and xinmailong(XML)on transverse aortic constrcition(TAC)-induced heart failure.Experiment 1Objective:Salvia miltiorrhiza is widely used in the treatment of heart disease in China..This research is aimed to find the mechanism of the effect of SalB,which is the main active ingredient of salvia miltiorrhiza,on curing heart failure.Methods:We created a mouse model of heart failure by inducing pressure overload with TAC surgery.AoPg,HR,LVAWd,LVPWd,LVIDd,LVAWs,LVPWs,LVIDs,EDV,ESV,EF%,FS%,LVW of echocardiography and BW,HW,LVW,LUW,LIW,TL,HW/BW,HW/TL,LVW/TL,LUW/BW and LIW/BW were used to evaluate the dynamic changes of cardiac structure and function in vivo.Plasma brain natriuretic peptide(BNP)concentration was detected by Elisa method.In addition,H9C2 rat cardiomyocytes were cultured and Western blot were implemented to evaluate the phosphorylation of ERK1/2,AKT,and protein expression of GATA4.Group:we compared among 4 study groups:SHAM group(n=10),TAC group(n=9),MET group(metprolol,positive drug treatment,n=9)and SalB group(SalB,240 mg·kg-1·day-1,n=9).Results:SalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2,not Ser473 site of AKT,leading to inhibit protein expression of GATA4 and plasma BNP(P<0.001),and inhibited heart failure at 2 weeks after TAC surgery.Conclusions:Our data provide evidence for SalB inhibits TAC induced heart failure via inactivating of ERK1/2/GATA4 signaling pathway.Experiment 2Objective:Xinmailong(XML)injection,a Chinese Medicine,is clinically effective in treating HF.However,the mechanism of XML's effectiveness on HF was unclear,and thus,was the target of the present study.Methods:We created a mouse model of heart failure by inducing pressure overload with TAC surgery.AoPg,HR,LVAWd,LVPWd,LVIDd,LVAWs,LVPWs,LVIDs,EDV,ESV,EF%,FS%,LVW of echocardiography and BW,HW,LVW,LUW,LIW,TL,HW/BW,HW/TL,LVW/TL,LUW/BW and LIW/BW were used to evaluate the dynamic changes of cardiac structure and function in vivo.In addition,H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2,AKT,GSK3? and protein expression of GATA4 in nucleus were detected with Western blot experiment.Group:we compared among 4 study groups:SHAM(n=10),TAC(n=12),MET(metoprolol,positive drug treatment,n=7)and XML(XML treatment,n=14).Results:XML reduced diastolic thickness of left ventricular posterior wall,increased ejection fraction and fraction shortening,so as to inhibit HF at 2 weeks after TAC.Moreover,XML inhibited the phosphorylation of ERK1/2,AKT and GSK3?,subsequently inhibiting protein expression of GATA4 in nucleus(P<0.001).Conclusions:XML inhibited the TAC-induced HF via inactivating the ERK1/2,AKT/GSK3?,and GATA4 signaling pathway.
Keywords/Search Tags:Pressure overload, Heart failure, Salvianolic acid B, Xinmailong
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