Effect of Metformin on Myocardial Firbosis in Model Rats / 医药导报

ABSTRACT

Objective To investigate the effects of metformin on myocardial fibrosis induced by isoproterenol(ISO) in rats and its mechanism. Methods A total of 48 SD male rats were randomly divided into four groups,normal control group,model control group,valsartan group and metformin group. Cardiac fibrosis models were induced in model group, Valsartan group and metformin group by subcutaneous injection of ISO 10 mg·kg-1·d-1in the 1stday, 5 mg·kg-1·d-1in the 2ndday, 3 mg·kg-1·d-1in the 3rd-10thday. Valsartan group and metformin group were fed valsartan 10 mg·kg-1, qd or metformin 100 mg·kg-1,bid for 28 days respectively.Rats were killed at the 3rdday,the 7thday,the 14thday and the 28thday.The value of HMI,LVMI,LVW/TL were measured,and pathological alteration were observed by HE staining and Masson staining,TGF-β and Smad3 protein expression in left ventricular myocardium were detected by western blotting,and IL-6 level in serum were detected by ELISA. Results The serum levels of IL-6 in control group, model group, valsartan group and metformin group were (59.18± 0.86) pg·mL-1, (71.90±1.35) pg·mL-1, (64.33±2.59) pg·mL-1and (65.45±1.92) pg·mL-1respectively on the 28th day. Compared with control group, the serum levels of IL-6 in model group were significantly increased(P<0.01), while their levels significantly reduced in rats received metformin (P<0.05). Conclusion Metformin may inhibit myocardial firbosis by TGF-β/Smads pathway.