Losartan reduces myocardial interstitial fibrosis in diabetic cardiomyopathy rats by inhibiting JAK/STAT signaling pathway

Purpose: This study was designed to investigate the effect of losartan on the myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) rats. Methods: In this study, a total of 48 male Wister rats (3 groups of 16 animals each) were examined, including the control group, DCM group and losartan-treated (DCM + L) group. Control group was fed with standard diet (14 KJ/g); DCM group and losartan-treated (DCM + L) group were both fed with high glucose and fat diet (20 KJ/g). Diabetes was induced by streptozotocin (STZ) intraperitoneal injuction (IP, 30 mg/kg body weight). Rats of DCM + L group were treated with losartan (30 mg/kg body weight) daily by oral gavage for 16 weeks. Biochemical, hemodynamic, histological and western blotting analyses were performed. Results: Compared with DCM rats, the quantity of p-JAK2 and p-STAT3 in myocardium of rats treated with losartan was lower, the expression of TGF-β1 was down-regulate, the content of collagen in myocardium decreased, LVSP and ± dp/dt increased, LVEDP decreased, the level of myocardial fibrosis reduced, and heart function improved evidently. Conclusion: Losartan has a protective effect on heart function against myocardial interstitial fibrosis of DCM by inhibiting JAK/STAT signaling pathway and lowering the expression of TGF-β1.