Effect Of Astragalus On Cardiomyocyte Apoptosis Pathways Caused By Doxorubicin In Rats With Dilated Cardiomyopathy

Objective:To clarify the role of Astragalus on cardiomyocyte apoptosis pathways in rats with dilated cardiomyopathy(DCM).To investigate the effects of Astragalus on cardiac function in rats with DCM.To reveal the possible mechanism of prevention and treatment of DCM by Astragalus.Methods:The establishment of DCM was icduced by intraperitoneal injection of doxorubicin(lmg/kg/model,2 times a week,12 times in all, observation 2 weeks).After 8weeks, the 95 rats were divided into Normal group(n= 14), DCM model group(n= 21), Perindopril group (n= 20), Metoprolol group (n= 20) and Astragalus group (n= 20).Perindopril was administered by gavage at a dose of 3mg/kg/model for Perindopril group.Metoprolol was administered by gavage at a dose of 50mg/kg,bid,in Metoprolol group.Astragalus was administered by gavage at a dose of 3.5mg/kg/model for Astragalus group.Distilled water was administered in Normal group and DCM model group.All of the rats were treated for 8weeks.After the treatment, the LVIDd、LVEDs、LVEF、FS were measured with echocardiography, the levels of serum BNP was tested by ELISA, and histopathological characteristics of left ventricular cardiac muscle were observed by HE.Apoptotic factors’ mRNAs (Bax、Bcl-2、Fas1、Fas、Caspase3) and Proteins(Bcl-2、Fas、Caspase3) in rat cardiac muscle were determined by RT-PCR and western blot.Results:1.the result of echocardiography:Compared with DCM model group, the LVIDd and LVIDs are decreased in Normal group and the treatment group, while the LVEF and FS are increased, P< 0.05.Compared with Perindopril group and Metoprolol group, the P value of LVIDd、LVIDs、FS in Astragalus group is more than 0.05, while the P value of LVEF is less than 0.05.2.Rats serum BNP levels:Compared with DCM model group, the serum BNP are decreased in Normal group and the treatment group, P< 0.05.Compared with Perindopril group and Metoprolol group, the P value of serum BNP levels in Astragalus group is more than 0.05.3.Rat myocardial HE staining:In Normal group, we can see normal myocardial cells, muscle fibers arranged in neat rows, structural integrity; nucleus clearly visible, round or oval; normal intercellular, no edema, even abundant cytoplasm, rich blood vessels in intercellular. In DCM model group, we can see myocardial cell swelling significantly; myocardial fibers disarray and broken, myocardial fibrosis obvious; pyknotic nuclei, deformation or disappear; intercellular edema, widened, partly granular or vacuolated degeneration; intercellular vascular dilatation and congestion, lymphocytes and monocytes occure. The myocardial fiber fracture, degree of fibrosis, intercellular edema and vacuolar degeneration are improved in treatment group.4.The expression of Bax、Bcl-2、Fas1、Fas、Caspase3 mRNA levels:Compared with DCM model group, the Bax、Caspase 3 mRNA are decreased(P< 0.05), while the Bcl-2 mRNA are increased in Normal group and the treatment group(P< 0.05), and the Fasl and Fas mRNA are decreased(P>0.05).5.The expression of Bax、Bcl-2、Fas1、Fas、Caspase3 protein levels:Compared with DCM model group, the Bcl-2 protein are increased in Normal group and the treatment group, while the Fas and Caspase 3 are decreased(P< 0.05).Compared with Perindopril group and Metoprolol group, the P value of Bcl-2、Fas、Caspase3 protein in Astragalus group is less than 0.05.Conclusion:1. Astragalus can effectively reduce the left ventricular Chamber diameter of rats with DCM, improve left ventricular contractility and reinforce myocardiac contractionreduce, reduce serum BNP level, protect damaged heart muscle tissue.2. Astragalus may partly regulate the expression of mRNA and protein of Bax, Bcl-2, Fas1, Fas and Caspase3 on myocardial tissue in rats with DCM.3.The mechanisms of rats with DCM treated with Astragalus may possibly by inhibiting apoptosis of cardiac muscle cells.Astragalus may have beneficial effect on DCM.