养心康片通过Akt/AMPK-mTOR通路对心肌梗死后心力衰竭模型兔心肌细胞自噬的影响

目的观察养心康片通过Akt/AMPK-mTOR通路对心肌梗死后心力衰竭模型兔心肌细胞自噬的影响。方法对实验兔应用结扎冠脉的方法建立心肌梗死后心力衰竭兔模型,随机分为模型组、养心康组、AMPK抑制剂组、Akt抑制剂组和mTOR抑制剂组。并另取不造模的兔设立空白对照组。每组5只,共30只。造模后第3天开始分别给予相应的处理措施,共4周。观察养心康片对模型兔心肌beclin 1、LC3蛋白表达,心肌beclin 1和Atg5 mRNA的表达的影响,电镜检测各组心肌细胞超微结构。结果养心康组的beclin 1 mRNA的表达量、beclin 1蛋白表达量较模型组、mTOR抑制剂组降低(P<0.05或P<0.01),较空白对照组、AMPK抑制剂组升高(P<0.05或P<0.01);养心康组的LC3-Ⅱ/LC3-I比值较模型组、mTOR抑制剂组降低(P<0.05),较空白对照组、AMPK抑制剂组升高(P<0.05)。养心康组的Atg5 mRNA表达量较模型组降低(P<0.05),较空白对照组、AMPK抑制剂组升高(P<0.05或P<0.01)。电镜结果显示养心康组的自噬体、自噬体溶酶体数量较模型组、Akt抑制剂组和mTOR抑制剂组降低减少,较AMPK抑制剂组增多。结论养心康片可通过干预Akt/AMPK-mTOR通路调控心肌细胞自噬水平,改善心肌梗死后心衰模型的心肌细胞超微结构。

Effects of Yangxinkang Tablet on Cardiomyocytes Autophagy in Rabbit with Heart Failure after Myocardial Infarction Through Akt/AMPK-mTOR Pathway

Objective To observe the effect of Yangxinkang Tablet on cardiomyocytes autophagy in rabbit with heart failure after myocardial infarction through Akt/AMPK-mTOR pathway.Methods The rabbit model of heart failure was established by ligation of coronary artery.The experimental animals were randomly divided into model group,Yangxinkang group,AMPK inhibitor group,Akt inhibitor group and mTOR inhibitor group,and the establishment of the blank control group,each group of 5,a total of 30.After the three days of modeling administration,were given the appropriate treatment measures,a total of 4 weeks.To observe the effects of Yangxinkang Tablet on expression of beclin 1,LC3 Protein and Expression of Beclin 1 and Atg5 mRNA in Cardiac Rabbits,Electron microscopy detected ultrastructure of myocardium.Results The expression of beclin 1 mRNA and beclin 1 protein in Yangxinkang group were lower than those in the model group and the mTOR inhibitor group(P<0.05 or P<0.01),and were higher than those in the blank control group and AMPK inhibitor group(P<0.05 or P<0.01).The ratio of LC3-Ⅱ/LC3-I in Yangxinkang group were lower than those in the model group and the mTOR inhibitor group(P<0.05),and were higher than those in the blank control group and AMPK inhibitor group(P<0.05).The expression of Atg5 mRNA in Yangxinkang group were lower than those in the model group(P<0.05),and were higher than those in the blank control group and AMPK inhibitor group(P<0.05 or P<0.01).Electron microscopy showed that the number of autophagosome and autophagosome lysosome of Yangxinkang group was lower than that of model group,Akt inhibitor group and mTOR inhibitor group,and more than that of AMPK inhibitor group.Conclusion Yangxinkang Tablet can regulate the cardiomyocytes autophagy level of through Akt/AMPK-mTOR pathway and improve the ultrastructure of myocardium in heart failure model after myocardial infarction.