Protective Effects of Andrographolide on Myocardial Injury in Rats with Sepsis via Regulation of the AMPK/mTOR Signaling Pathway
Objective:To investigate the protective effects of andrographolide on myocardial injury in rats with sepsis and its impact on the adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapa-mycin(mTOR)signaling pathway.Methods:Rats were randomly divided into five groups:sepsis group,androgra-pholide group,AMPK pathway inhibitor(Compound C)group,andrographolide+Compound C group,and control group,with 12 rats in each group.Except for the control group,the other groups were subjected to cecal ligation and puncture to induce sepsis,with a 100％success rate.After successful modeling,the rats were treated with drugs once daily for 7 days.Changes in left ventricular end-systolic diameter(LVDs),fractional shortening(FS),and left ventricular ejection fraction(LVEF)were measured.Levels of creatine kinase MB(CK-MB)and cardiac troponin Ⅰ(cTnⅠ)in serum were detected by ELISA.Histopathology of myocardial tissue was examined by HE staining.The number of autophagosomes in myocardial tissue was observed by transmission electron microscopy.Cell apoptosis in myocardial tissue was detected by TUNEL staining.Expression of microtubule-associated protein 1 light chain 3(LC3),Bel-2-associated X protein(Bax),p-AMPK,and p-mTOR proteins in myocardial tissue was detected by Western blotting.Results:Compared with the sepsis group,myocardial injury in the androgra-pholide group was alleviated,as evidenced by decreased LVDs,serum cTnⅠ and CK-MB levels,myocardial cell apoptosis rate,and Bax and p-mTOR protein levels,and increased FS,LVEF,number of autophagosomes,LC3-Ⅱ/LC3-Ⅰ ratio,and p-AMPK protein levels.The changes in these indicators in the Compound C group were oppo-site to those in the andrographolide group(P＜0.05).Compound C reversed the effects of andrographolide on au-tophagy and myocardial cell apoptosis in rats with sepsis-induced myocardial injury.Conclusion:Androgra-pholide may protect against sepsis-induced myocardial injury in rats by activating AMPK and downregulating the mTOR pathway,thereby promoting autophagy and inhibiting myocardial cell apoptosis.
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