Polydatin attenuates acute myocardial infarction-induced myocardial fibrosis by inhibiting the TGF-β/Smad/ERK signaling pathway
The aim of this research was to investigate the pharmaceutical effect of polydatin(PD)on the amelioration of acute myocardial infarction(AMI)-induced myocardial fibrosis in rat model.To this end,SD rats were randomly divided into control group( Ct),model group( Model),low-dose PD treatment group( PD-L,40 mg/kg),high-dose PD treatment group( PD- H,100 mg/kg),captopril treatment group(CTP,20 mg/kg),and PD-H + TGF-β agonist group(100 mg/kg+30 mg/kg).AMI was induced by left anterior descending coronary artery ligation in all rats except those in the Ct group.Myocardial function and tissue structure were evaluated by animal ultrasound system and Masson staining of the heart.The collagen sedimentation in the myocardial tissue was evaluated by immunohistochemistry and the levels of IL-6 and TNF-α were measured by ELISA kits.The protein expressions of TGF-β1,p-Smad2/3,and p-ERK1/2 were assessed by Western blotting.Compared to those in the Ct group,rats in the model group exhibited worse myocardial function with severe myocardial fibrosis and systematic inflam-matory responses(all P ＜0.05).Notably,PD treatment significantly ameliorated AMI-induced myocardial injury in a dose-dependent manner,evidenced by improved myocardial function,less fibrotic collagen deposition,less inflammatory factors secretion along with the inhibition of the TGF-β/Smad/ERK signaling pathway(all P＜0.05).Moreover,the therapeutic effect of high-dose PD was comparable to that of positive control captopril whereas SRI-011381(a type of TGF-β agonist)remarkedly abrogated the rescue effect of PD on the AMI-induced myocardial fibrosis.In conclusion,our study demonstrates that PD may relieve the degree of myocardial inflammatory infiltration and improve AMI-induced myocardial fibrosis in rats by inhibiting the TGF-β/Smad/ERK signaling pathway,which may promote damaged myocardium repairments.
polydatinacute myocardial infarctionmyocardial fibrosistransforming growth factor βextracellular regulated protein kinase
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维普
