Valsartan Inhibits Myocardial Apoptosis by Down-regulating Myocardial X-box Binding Protein 1 Expression in Experimental Diabetic Cardiomyopathy Rat’s Model / 中国循环杂志

ABSTRACT

Objective: To study the relationship between myocardial X-box binding protein 1 (XBP1) expression and myocardial apoptosis in experimental diabetic cardiomyopathy (DCM) rat’s model and to clarify the mechanism of valsartan inhibiting myocardial apoptosis. Methods: A total of 50 Wistar rats were divided into 2 groups Control group, the rats received intraperitoneal citrate buffer at 65mg/kg,n=10 and Streptozotocin group, the rats received intraperitoneal streptozotocin at 65mg/kg,n=40, all animals were treated for 7 days. DCM model was established in 37 rats (fasting blood glucose ≥ 16.7mmole/L) and they were further divided into 2 groups DCM group, the rats received intragastric normal saline,n=20 and DCM + valsartan group, the rats received intragastric valsartan at 30mg/kg·day,n=17. The rats were treated for 16 weeks. The body weight, tail blood pressure, glucose and cardiac function were compared among 3 groups. Myocardial apoptosis was detected by TUNEL staining, RNA and protein expressions of myocardial cytochrome C, cleaved caspase 3, glucose regulation protein 78 (GRP78) and XBP1-s were examined by immunolfuorescence, real time RT-PCR and Western blot analysis. Results: Compared with Control group, DCM group showed disordered cardiac structure, more collagen content and myocardial apoptosis,P<0.05; increased RNA and protein expressions of GRP78, XBP1-s, cleaved caspase 3 and cytochrome C,P<0.05. Compared with DCM group, DCM + valsartan group had rather regularly arranged myocardiocytes, less interstitial ifbrosis and myocardial apoptosis,P<0.05; decreased RNA and protein expressions of GRP78, XBP1-s, cleaved caspase 3 and cytochrome C,P<0.05. Conclusion: Valsartan may inhibit myocardial XBP1 activation and therefore, reduce the myocardial apoptosis in experimental DCM rat’s model.