厄贝沙坦对糖尿病大鼠心肌损伤中Notch1信号通路的影响

doi:10.12047/j.cjap.5674.2018.097

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (5): 427-431.doi: 10.12047/j.cjap.5674.2018.097

厄贝沙坦对糖尿病大鼠心肌损伤中Notch1信号通路的影响

张恒¹, 陶敏^1,2, 康品方^1,2, 郭建路^1,2, 宣玲¹, 高琴^2,3, 唐碧¹, 李路佳⁴, 王洪巨¹

1. 蚌埠医学院第一附属医院心血管科, 安徽蚌埠 233004;
2. 蚌埠医学院科研中心, 安徽蚌埠 233030;
3. 蚌埠医学院生理学教研室, 安徽蚌埠 233030;
4. 蚌埠医学院临床医学院, 第一分党委, 安徽蚌埠 233030

收稿日期:2018-01-23 修回日期:2018-09-25 出版日期:2018-09-28 发布日期:2019-02-21
通讯作者: 王洪巨,Tel:0552-3086103;E-mail:docwhj1101@163.com E-mail:docwhj1101@163.com
基金资助:
国家自然科学基金（81550036，81770297）；安徽省教育厅重点项目（KJ2016A484）；高校学科（专业）拔尖人才学术资助重点项目（gxbjZD2016072）；省级大学生创业创新计划（201710367052）

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

ZHANG Heng¹, TAO Min^1,2, KANG Pin-fang^1,2, GUO Jian-lu^1,2, XUAN Ling¹, GAO Qin^2,3, TANG Bi¹, LI Lu-jia⁴, WANG Hong-ju¹

1. Department of Cardiovascular Medicine, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004;
2. Science Research Centre, Bengbu 233004;
3. Department of Physiology, Bengbu Medical College, Bengbu 233004;
4. Department of Clinical Medical College, the First Branch Party Committee of Bengbu Medical College, Bengbu 233030, China

Received:2018-01-23 Revised:2018-09-25 Online:2018-09-28 Published:2019-02-21
Supported by:
国家自然科学基金（81550036，81770297）；安徽省教育厅重点项目（KJ2016A484）；高校学科（专业）拔尖人才学术资助重点项目（gxbjZD2016072）；省级大学生创业创新计划（201710367052）

摘要/Abstract

摘要： 目的：观察厄贝沙坦对糖尿病大鼠心肌损伤的作用，分析Notch1信号通路在其中的变化。方法：实验分4组：正常对照组（CON）、高糖高脂组（HC）、糖尿病组（DM）和厄贝沙坦+糖尿病组（Ir+DM）。制作2型糖尿病（T2DM）大鼠模型成功后，第8周开始检测大鼠空腹血糖水平（FBG）、全心质量及左心室重量，计算心脏指数（H/B）及左室重量指数（LVWI），检测大鼠血浆甘油三酯（TG）、胆固醇（TC）水平，检测心肌组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量变化，免疫组化检测Bcl-2、Bax表达变化，Western blot检测大鼠心肌组织Notch1、Hes-1及Jagged-1的蛋白表达。结果：与CON组相比，HC组H/B、LVWI、FBG无明显变化，血脂、MDA含量明显升高，SOD活性、Bcl-2/Bax及Notch1、Hes-1、Jagged-1蛋白表达降低；与HC组相比，DM组H/B、LVWI、FBG、MDA含量增加明显，血脂水平无明显变化，SOD活性、Bcl-2/Bax及Notch1信号通路蛋白表达进一步降低；与DM组相比，厄贝沙坦干预组H/B、LVWI明显降低，血脂、血糖水平无明显变化，但SOD活性、Bcl-2/Bax增加，MDA含量降低，同时Notch1信号通路相关蛋白表达增加。结论：糖尿病可导致大鼠发生心肌损伤，厄贝沙坦可能通过增强Notch1信号通路的表达发挥心肌保护作用。

关键词: 厄贝沙坦, 糖尿病, 大鼠, 心肌损伤, Notch1信号通路

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

张恒, 陶敏, 康品方, 郭建路, 宣玲, 高琴, 唐碧, 李路佳, 王洪巨. 厄贝沙坦对糖尿病大鼠心肌损伤中Notch1信号通路的影响[J]. 中国应用生理学杂志, 2018, 34(5): 427-431.

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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厄贝沙坦对糖尿病大鼠心肌损伤中Notch1信号通路的影响

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

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