Study on the Protective Effect and Mechanism of Monoester Alkaloids on Cardiomyocytes of CHF Rats
Objective To analyze the protective effects of single ester alkaloids on myocardial cells of chronic heart failure rats and their effects on PI3K/AKT pathway.Method 100 rats were randomly divided into group A(blank group),group B(model group),group C(low-dose group),group D(medium-dose group)and group E(high-dose group)with 20 rats in each group.Groups C,D and E were given aconite concentrate by intragastric administration after successful modeling of chronic heart failure model,and the doses were 2.79,5.57 and 11.14 g/kg,respectively.After 6 weeks of gavage,histopathological changes,echocardiographic examination indexes,myocardial cell apoptosis rate,expression of cardiac tissue proapoptotic protein(Bax),B-lymphoblastoma-2(Bcl-2),Cagpase-8,autophagy protein,BNP,AI of myocardial cells in each group were observed.Result The echocardiography indexes IVSs,IVSd,LVPWs,LVPWd,the apoptosis rate of cardiomyocytes,the expression of Bax,Caspase-8,the levels of IL-6,TNF-α,the expression of autophagy protein LC3-Ⅱ,LC3-Ⅱ/Ⅰ,BNP and AI in cardiomyocytes in groups E,D and C were higher than those in group A.LVEF,expressions of Bcl-2,PO2,autophagy protein P62,p-PI3K and p-AKT in groups E,D and C were lower than those in group A(P<0.05).The IVSs,IVSd,LVPWs,LVPWd,the apoptosis rate of myocardial cells,the expression of Bax and Caspase-8,levels of IL-6,TNF-α,autophagy protein LC3-Ⅱ,LC3-Ⅱ/Ⅰ,BNP and AI in groups E,D and C were lower than those in group B.LVEF,the expressions of Bcl-2,PO2,autophagy protein P62,P-PI3K and P-Akt in groups E,D and C were higher than those in group B(P<0.05).With the increase of concentration of monkshood concentrate,IVSs,IVSd,LVPWs,LVPWd,myocardial cell apoptosis rate,Bax,Caspase-8 expression,IL-6,TNF-α levels,myocardial autophagy protein LC3-Ⅱ,LC3-Ⅱ/Ⅰ,BNP and AI levels decreased.LVEF,the expressions of Bcl-2,PO2,autophagy protein P62,p-PI3K and p-AKT in myocardial cells were increased(P<0.05).Conclusion Single ester alkaloids may activate PI3K/AKT pathway by up-regulating the expression of p-PI3K and p-AKT,and alleviate the malignant progression of heart failure in a dose-dependent manner.
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