Zhang Heng, Tao Min, Kang Pin-Fang, Guo Jian-Lu, Xuan Ling, Gao Qin, Tang Bi, Li Lu-Jia, Wang Hong-Ju
Department of Cardiovascular Medicine, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004.
Science Research Centre, Bengbu 233004.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 May 8;34(5):427-431. doi: 10.12047/j.cjap.5674.2018.097.
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.
Thirty rats were randomly divided into four groups:normal control group (CON, =6), high calorie group (HC, =6) and diabetes mellitus group (DM, =9), irbesartan + diabetes group (Ir + DM, =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.
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.
Diabetes can induce myocardial injury, and irbesartan has myocardial protective effects through activation of Notch1.
探讨厄贝沙坦对糖尿病大鼠心肌损伤的影响及其机制，并分析其中Notch1信号通路的变化。
将30只大鼠随机分为四组：正常对照组（CON，n = 6）、高热量组（HC，n = 6）、糖尿病组（DM，n = 9）、厄贝沙坦 + 糖尿病组（Ir + DM，n = 9）。造模8周后，测量体重比和左心室重量指数，并用自动生化分析仪检测血清甘油三酯（TG）和总胆固醇（TC）水平。采用试剂盒测定大鼠心肌中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量的变化，用免疫组织化学法检测心肌中B细胞淋巴瘤-2（Bcl-2）和Bcl-2相关X蛋白（Bax）蛋白的表达。用蛋白质免疫印迹法检测大鼠心肌中Notch1、Hes-1和Jagged-1的表达。
与CON组相比，HC组心脏重量/体重（H/B）、左心室重量指数（LVWI）和空腹血糖（FBG）水平无明显变化，而血脂、MDA和Bax水平显著升高，SOD、Bcl-2以及Notch1、Hes-1和Jagged-1的表达降低。与HC组相比，DM组H/B、LVWI、FBG、MDA和Bax水平显著升高，SOD、Bcl-2以及Notch1、Hes-1和Jagged-1水平降低。Ir + DM组H/B、LVWI、Notch1、Hes-1和Jagged-1的表达升高，但其他指标差异无统计学意义。Ir + DM组H/B和LVWI显著低于DM组，血脂和血糖水平无明显变化，但氧化应激和细胞凋亡发生率降低。而Notch-1、Hes-1、Jagged-1蛋白表达升高。
糖尿病可诱导心肌损伤，厄贝沙坦通过激活Notch1发挥心肌保护作用。
