Effects of irbesartan on Notch1 signaling pathway in diabetic rats with myocardial injury

doi:10.12047/j.cjap.5674.2018.097

Abstract

Abstract: Objective: To investigate the effects and mechanisms of irbesartan on myocardial injury in diabetic rats, and to analyze the changes of Notch1 signaling pathway in it. Methods: Thirty rats were randomly divided into four groups:normal control group (CON, n=6), high calorie group (HC, n=6) and diabetes mellitus group (DM, n=9), irbesartan + diabetes group (Ir + DM, n=9). After modeling 8 weeks later, the body weight ratio and left ventricular weight index were measured and the serum levels of triglyceride (TG) and total cholesterol (TC) were measured by automatic biochemical analyzer. The changes of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium of rats were determined by the kit and the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 assaciated X protein (Bax) protein in myocardium were detected by immunohistochemistry. The expressions of Notch1, Hes-1 and jagged-1 in myocardium of rats were detected by Western blot. Results: Compared with CON group, the levels of heart weight/body weight (H/B), left ventricular weight index(LVWI) and fasting blood glucose(FBG) in HC group were not significantly changed, while the levels of blood lipids, MDA and Bax were increased significantly, and the expressions of SOD, Bcl-2 and Notch1, Hes-1 and Jagged-1 were decreased. Compared with HC group, the levels of H/B, LVWI, FBG, MDA and Bax in DM group were increased significantly, and the levels of SOD, Bcl-2 and Notch1, Hes-1 and Jagged-1 were decreased. The expression of H/B, LVWI, Notch1, Hes-1 and Jagged-1 in Ir+DM group were increased, but there was no significant difference between the other indexes. The H/B and LVWI in Ir + DM group were significantly lower than those in DM group, the levels of blood lipid and blood glucose did not change significantly, but the incidence of oxidative stress and apoptosis was reduced. While Notch1, Hes-1, Jagged -1 protein expressions were increased. Conclusion: Diabetes can induce myocardial injury, and irbesartan has myocardial protective effects through activation of Notch1.

Key words: irbesartan, diabetic, rats, myocardial injury, Notch1 signaling pathway

ZHANG Heng, TAO Min, KANG Pin-fang, GUO Jian-lu, XUAN Ling, GAO Qin, TANG Bi, LI Lu-jia, WANG Hong-ju. Effects of irbesartan on Notch1 signaling pathway in diabetic rats with myocardial injury[J]. CJAP, 2018, 34(5): 427-431.

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