Effect and Mechanism of Sacubitril/valsartan on Ventricular Remodeling in STZ induced Diabetic Cardiomyopathy Rats

Abstract

Background: Diabetic cardiomyopathy (DCM) has a high incidence of heart failure and poor prognosis, so its prevention and treatment should be more active. In this study, we investigate the effect and mechanism of sacubitril/valsartan (Sac/Val) on ventricular remodeling in DCM rats, so as to provide a new idea for clinical prevention of DCM.Methods: Twenty 8-week-old male Wistar rats were randomly divided into four groups: normal rat group (NOR), DCM group, DCM+ Sac/Val group and DCM+ Perindopril (PER) group , with 5 rats in each group. The DCM rat model was established by intraperitoneal injection of 1% streptozotocin (STZ). NOR and DCM groups were gavaged with normal saline (1ml/100g/d) for 8 weeks, while Sac/Val and PER groups were gavaged with Sac/Val (60mg/kg/d) and PER (2mg/kg/d) for 8 weeks. HE and Masson staining were used to evaluate the pathological changes of myocardial tissue, the left ventricular/ body mass index was calculated to evaluate ventricular remodeling, the levels of IL-6 and TNF- α in myocardial tissue were detected by ELISA, and the protein expression of p-38 and phos-p38 was detected. Results: Compared with the NOR group, the arrangement of cardio myocytes in the DCM group was disordered and the content of collagen fibers increased. In the DCM group, the left ventricular/body mass index increased, the levels of IL-6 and TNF- α increased, and the phos-p38 protein expression increased (P＜0.01). Compared with DCM group, fewer collagen fibers were found and the degree of fibrosis was reduced in Sac/Val group and PER group. The levels of left ventricular/body mass index, IL-6, TNF- α and phos-p38 protein expression in the Sac/Val group were all lower than those in the DCM group, and the differences were statistically significant (P＜0.01).Conclusion: Sac/Val can improve ventricular remodeling in DCM, and its mechanism may be related to its anti-inflammatory effect and inhibition of p38 signaling pathway in myocardial tissue.