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Study On Effects And Mechanisms Of Compound Astragalus Mixture Nourishing Heart To Reperfusion Arrhythmias And Cardiac Remodeling In Rats

Posted on:2014-06-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q L ChenFull Text:PDF
GTID:1264330398492025Subject:TCM clinical basis
Abstract/Summary:PDF Full Text Request
Objective To study the effects of Compound Astragalus Mixture Nourishing Heart (CAMNH) on reperfusion arrhythmia(RA) and myocardial connexin43(Cx43) in male sprague dawley(SD) rats of ischemia/reperfusion injury(I/R) after coronary artery ligation, and to explore the relationship between RA and myocardial Cx43in the first part of this study.To study the effects of CAMNH on ultrasonic cardiogram(UCG), myocardial and perivascular collagen fibration, and myocardial Cx43in SD rats of cardiac remodeling(VR) after coronary artery ligation, and to explore the relationship between myocardial and perivascular collagen fibration and myocardial Cx43in the second part of this study.MethodIn the first part, the following method were adopted. SD rats were were randomly divided into6groups, as high-dose group of CAMNH(CAMNHh),medial-dose group of CAMNH(CAMNHm), low-dose group of CAMNH(CAMNH1), MSSRT group, I/R group and sham-operated(SO) group. Then the rats were treated for14days with CAMNHh(28g·1kg-1·d-1), CAMNHm(14g·1kg-1·d-1), CAMNH1(7g·1kg-1·d-1) or Metoprolol Succinate Sustained-Release Tablets(MSSRT,9.5mg·1kg-1·d-1) before acute myocardial infarction(AMI). AMI was induced by ligation of Left Anterior Descending(LAD) coronary artery for30mins, followed by reperfusion of60mins. The ventricular arrhythmia(VA) score.The distribution and expression of myocardial Cx43were observed with immunehistochemistry(IHC). Average optical density of myocardial Cx43(myocardial Cx43-AOD) were measured with Image Pro Plus6.0. The correlation between VA score and myocardial Cx43-AOD in the ischemic regions was analyzed.In the second part, the following method were adopted. Watched10days after ligation of LAD coronary artery, the survived rats were randomly divided into5groups, as CAMNHh group, CAMNHm group, CAMNH1group, MSSRT group and VR group. The other group was SO group. Then the rats were treated for8weeks with CAMNHh(28g·1kg-1·d-1), CAMNHm (14g·1kg-1·d-1),CAMNH1(7g·1kg-1·d-1) or MSSRT(9.5mg·1kg-1·d-1). On the end of the sixth week and the tenth week after ligation of LAD coronary artery, diameter of left ventricle at end-systole(LVDs, mm), left ventricular eject fractions(LVEF,%) and fraction shortening (FS,%) were measured with UCG. Then to compare the change between the sixth week and the tenth week after ligation, and to compare the amplitude of variation among groups. At the end of the experiment, the ratio of weight(Wt,g) and ventricle weight(Vt,g), Vt/Wt(%) was calculated. The VR of rats were observed with upgrading Masson, then collagen volume fraction(CVF,%) and perivascular collagenvolume area(PVCA,%) were measured with Image Pro Plus6.0. The distribution of myocardial Cx43were observed with IHC, and the ratio of myocardial Cx43(myocardial Cx43-T,%) were detected with western blot(WB). The relative content of myocardial Cx43was measured by Quantity One1-D Analysis Software. CVF(%) and PVCA(%) were used to analyze the correlation with myocardial Cx43-T(%) in the non infarct regions.ResultIn the first part, the following results were obtained. The VA score of CAMNH1group and MSSRT group was less than I/R group. Most of the infarction regions and ischemic regions were located in subendocardial myocardium, and the non ischemic regions in midmyocardium. CAMNHm group, CAMNH1and MSSRT group vs I/R group, the change of the distribution of myocardial Cx43was modified, and myocardial Cx43-AOD(%) in ischemic region were inVReased(P<0.05). There were negative correlation between the VA score and myocardial Cx43-AOD(%) in ischemic region(P<0.05).In the second part, the following results were obtained. On the end of the sixth week after ligation, the following results were gotten with UCG. CAMNHm group and CAMNH1group vs MSSRT group, LVEF (%) and FS(%) deVReased (P<0.05). CAMNHm group and CAMNH1group vs VR group, LVEF (%) and FS(%) didn’t deVRease (P>0.05). Then on the end of the tenth week, LVDs(mm), LVEF (%) and FS(%) were obtained. VR group vs MSSRT group, VR group vs CAMNHm group, LVDs(mm) significantly inVReased (P<0.01). VR group vs CAMNH1group, LVDs(mm) inVReased (P<0.05). VR group vs MSSRT group, CAMNHm group, and CAMNH1group, LVEF (%) and FS(%) significantly reduced (P<0.01). When comparing the change between the sixth week and the tenth week after ligation, it was found that LVDs(mm) inVReased in VR group(P<0.05), LVEF (%) and FS(%) significantly reduced in VR group and MSSRT group (P<0.01). After comparing VR group with the other groups, the inVRescent amplitudes of LVDs(Δ LVDs, mm) significantly inVReased(P<0.01), and the reduced amplitude of LVEF(Δ LVEF,%) and FS(ΔFS,%) significantly inVReased(P<0.01).CAMNHm group and CAMNH1group vs VR group, Vt/Wt(%) significantly deVReased(P<0.01). MSSRT group vs VR group, Vt/Wt(%) deVReased(P<0.05). MSSRT group, CAMNHm group and CAMNH1group vs VR group, CVF(%) and PVCA(%) significantly deVReased(P<0.01). The expression of myocardial Cx43in non infarction region slightly reduced. VR group vs MSSRT group and CAMNH1group, myocardial Cx43-T(%) in non infarction region significantly deVReased(P<0.01), and VR group vs CAMNHh group, VR group vs CAMNHm group, deVReased(P<0.05). CVF(%) and PCVA(%)were negatively correlated significantly with myocardial Cx43-T(%) in non ischemic region(P<0.01).ConclusionIn the first part, the following conclusions are reached. CAMNH1induce VA score, the effects are similar to MSSRT. Most of the infarction region and ischemic region locate in subendocardial myocardium, and the non ischemic region in midmyocardium. CAMNHm and CAMNH1can inVReases the expression of myocardial Cx43in ischemic region, and the effects is near to MSSRT. There were negative correlation between the VA score and myocardial Cx43-AOD(%) in ischemic region.In the second part, the following conclusions can be gotten. CAMNHm and CAMNH1can persistently ameliorate the acVRetion of LVDs(mm) and the reduction of LVEF(%) and FS(%), and the effects is near to MSSRT. CAMNHm and CAMNH1can reduce Vt/Wt(%), and the effects is near to MSSRT. CAMNHh, CAMNHm and CAMNH1can reduce CVF(%), PVCA(%) and myocardial Cx43-T(%)in non infarction region. The effects are near to MSSRT and no dose-dependent. CVF(%) and PCVA(%) are negatively correlated significantly with myocardial Cx43-T(%) in non ischemic region.
Keywords/Search Tags:compound astragalus mixture nourishing heart, myocardial reperfusion, connexin43, arrhythmia, metoprolol, cardiac remodeling
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