Losartan reduces myocardial interstitial fibrosis in diabetic cardiomyopathy rats by inhibiting JAK/STAT signaling pathway.
Lijun Wanga, Juan Lib, Dajun Lic
- aDepartment of General Surgery, Tianjin Hospital China
- bTianjin Medical Examination Service, Tianjin Health Human Resources Service China
- cFirst Teaching Hospital of Tianjin University of Traditional Chinese Medicine China
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Abstract
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.