Abstract
Objective:To investigate the effect of Acacetin on on myocardial damage in rats with myocardial infarction(MI)by regulating the stress-induced protein 2(sestrin2)/AMP-activated protein kinase(AMPK)signaling pathway.Methods:A MI rat model was constructed by left anterior descending coronary artery ligation method,75 successfully modeled rats were randomly assigned into Model group,low-dose Acacetin(L-Acacetin,12.5 mg/kg)group,medium-dose Acacetin(M-Acacetin,25 mg/kg)group,high-dose Acacetin(H-Acacetin,50 mg/kg)group,H-Acacetin+sestrin2 inhibitor(sh-sestrin2)group,with 15 rats in each group.Additionally,15 rats were selected respectively as control(CK)group and the Sham operation(Sham)group.Ultrasound elec-trocardiogram,TTC staining,HE staining,Masson staining,ELISA and Western blot were used to detect rat heart function,MI area,pathological damage of myocardial tissue,fibrosis around myocardial infarction,inflammatory factors,and levels of sestrin2/AMPK signaling pathway related proteins.Results:Rats in CK and Sham groups did not experience MI and had regular arrangement of myo-cardial cells,without inflammatory cell infiltration or collagen fiber deposition.Compared with CK group,there was no great difference in expressions of LVSP,LVEF,LVEDP,LVESV,IL-8,IL-1β,TNF-α,sestrin2 and p-AMPK/AMPK proteins in Sham group(P>0.05).MI area of rats in Model group was increased,arrangement of myocardial cells was disordered,and there was severe inflamma-tory cell infiltration and collagen fiber deposition.LVSP,LVEF,expressions of sestrin2 and p-AMPK/AMPK proteins were decreased in Model group compared to Sham group,while LVEDP,LVESV,levels of IL-8,IL-1β and TNF-α were increased(P<0.05).Com-pared with Model group,LVSP,LVEF,expressions of sestrin2 and p-AMPK/AMPK proteins were increased in each dose Acacetin groups,while LVEDP,LVESV,MI area,myocardial tissue patholo-gical damage,collagen fiber deposition,levels of IL-8,IL-1β and TNF-α were decreased(P<0.05).Compared with H-Acacetin group,LVSP,LVEF,expressions of sestrin2 and p-AMPK/AMPK proteins were greatly reduced in H-Acacetin+sh-sestrin2 group,while LVEDP,LVESV,MI area,myocardial tissue pathological dam-age,collagen fiber deposition,levels of IL-8,IL-1β and TNF-α were greatly increased(P<0.05).Conclusion:Improvement of Acac-etin on myocardial damage in MI rats may be related to the activation of sestrin2/AMPK signaling pathway.关键词
刺槐素/Sestrin2/AMPK信号通路/心肌梗死/心肌损伤Key words
Acacetin/Sestrin2/AMPK signaling pathway/Myocardial infarction/Myocardial damage分类
医药卫生
