Effect And Underlying Mechanism Of Rxra Agonist Bexarotene On Cardiac Structure And Function In Diabetic Rats

Objectives: To explore the effect and underlying mechanism of bexarotene, the agonist of retinoid X receptor, on the structure and function of the heart in the streptozotocin (STZ)-induced diabetic rats. Methods: 40 SD rats were randomly divided into four groups:normal control group, intraperitoneal injection of citrate buffer (0.1 ml/100 g); diabetic group (DM), intraperitoneal injection of STZ (60 mg/Kg); DM+Bex (10 mg/kg /d); DM + Bex (20 mg/kg/d), 10 in each group. Results: Fasting blood glucose levels in DM group were significantly higher than that in control (p < 0.01); The blood glucose in DM+Bex (20 mg/kg/d) group decreased significantly from baseline after 4 weeks Bex intervention (p < 0.01). RXRα agonist bexarotene inhibited the effects of DM on these parameters in a dose-dependent manner. IVSd and LVPWd were significantly lower in DM group than that in control group and were significantly increased in DM+Bex (20 mg/kg/d) group compared with DM group (p < 0.01). Bex intervention could significantly improve left ventricular longitudinal strain, stratified longitudinal strain and longitudinal strain rate (SrL) in a concentration-dependent. Compared with the control group, myocardial apoptosis proteins (Bcl2 and Bax) expression levels and myocardial apoptosis rate were increased significantly in DM group. Bcl2/Bax ratio in DM rats was significantly lower than that in controls (p < 0.01). Conclusion: RXRα agonists bexarotene improves cardiac structure and function in STZ-induced diabetic rats through lowering blood sugar, inhibition of cardiomyocyte apoptosis and ventricular remodeling; Myocardial longitudinal velocity and two-dimensional strain are more sensitive to detect the early abnormality of systolic and diastolic function than conventional two-dimensional echocardiography in STZ-induced diabetic rats.