| Aim of the study:To explore whether Hyperoside(Hyp)can counteract myocardial infarction(MI)-induced cardiomyocyte injury by modulating JAK2/STAT3 signaling pathway and its potential mechanism.Methods: In vivo experiments,the myocardial infarction model was constructed by ligating the left anterior descending coronary artery(LAD)of male C57BL/6 mice.They were divided into seven groups: sham group,MI group,MI+Hyp(9 mg/kg),MI+Hyp(18 mg/kg)group,MI+Hyp(36 mg/kg)group,MI+Captopril group(15 mg/kg)group and MI+Hyp(36 mg/kg)+AG490(7.5 mg/kg)group.The contents of ECG,echocardiogram and myocardial injury markers in serum of mice were detected 14 days after group administration.HE staining,Masson staining and Sirius Red staining were used to detect the myocardial histopathological changes.TTC and TUNEL staining were used to observe myocardial infarction size and myocardial cell apoptosis in mice.The expressions of JAK2/STAT3 signaling pathway,apoptosis and autophagy related proteins in myocardial tissue were measured by Western Blot.In vitro experiments,the model of myocardial ischemia and hypoxia was established by oxygen glucose deprivation(OGD)inducing rat H9c2 myocardial cell damage.In vitro experiments were divided in seven groups: Control group,OGD group,OGD+Hyp(20 μM)group,OGD+Hyp(40 μM)group,OGD+Hyp(80 μM),OGD+Captopril(10 μM)group and OGD+Hyp(80 μM)+AG490(100 μM)group.LDH release,MDA content and SOD activity in the nutrient solution of cardiomyocytes were measured after 12 h of OGD treatment;ROS levels in cardiomyocytes were tested by immunofluorescence.Cardiomyocyte apoptosis was detected by flow cytometry,and the proteins associated with JAK2/STAT3 signalling pathway,apoptosis and autophagy in cardiomyocytes were examined by Western Blot.Results:In vivo experiments,Hyp can restore MI-induced ECG changes in mice,reduce serum c Tn I content,CK-MB and LDH activity,and improve cardiac function;it can also reduce myocardial fibrosis,infarct size and cardiomyocyte apoptosis in the infarcted area.The experimental results in vitro show that Hyp can reduce OGD-induced ROS and oxidative stress levels and counteract the apoptosis.Meanwhile,the protein expressions of p-JAK2/T-JAK2 and p-STAT3/T-STAT3 were checked by Western Blot,it was found that Hyp activated the JAK2/STAT3 signaling pathway in vitro and in vivo.Moreover,the JAK2/STAT3 signaling pathway inhibitor AG490 can reverse the above effects of Hyp.It indicated that the protective effect of Hyp on cardiomyocyte injury was,at least partly,through the regulation of JAK2/STAT3 signaling pathway.Conclusion: Hyp can alleviate myocardial cell injury induced by MI or OGD via activating JAK2/STAT3 signal pathway. |
