Apelin-13通过eNOS/NO促进糖尿病小鼠主动脉细胞焦亡相关蛋白的表达

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (2): 155-160.

Apelin-13通过eNOS/NO促进糖尿病小鼠主动脉细胞焦亡相关蛋白的表达

王炀佳, 张佳, 李宾, 曾翔俊^*

首都医科大学生理学与病理生理学系, 北京 100069

收稿日期:2018-11-30 修回日期:2019-03-28 出版日期:2020-02-05 发布日期:2020-02-05
通讯作者: ^*megan_zeng@163.com
基金资助:
国家自然科学基金(81270815)

Apelin-13 promotes expression of pyroptosis related protein in aortic cells in diabetic mice through eNOS/NO pathway

WANG Yang-jia, ZHANG Jia, LI Bin, ZENG Xiang-jun^*

Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, China

Received:2018-11-30 Revised:2019-03-28 Online:2020-02-05 Published:2020-02-05
Contact: ^*megan_zeng@163.com

摘要/Abstract

摘要： 目的探讨血管活性多肽apelin-13是否通过eNOS/NO途径影响糖尿病小鼠主动脉细胞焦亡相关蛋白的表达。方法以8周龄C57/BL小鼠作为对照组小鼠;以8周龄kkAy小鼠作为2型糖尿病小鼠模型。给糖尿病小鼠皮下埋植缓释泵,持续灌注apelin-13 处理14 d,剂量为30 μg/(kg·d)或apelin-13和L-NAME[NG-nitro-L-arginine methyl ester, L-NAME, eNOS抑制剂,剂量为10 mg/(kg·d)]共同处理14 d。用无创尾压法检测各组小鼠处理前后的血压值;取血检测血糖和糖化血红蛋白;取腹主动脉,进行HE染色,显微镜下观察血管形态学改变,免疫组织化学染色分析小鼠主动脉内eNOS和细胞焦亡相关信号蛋白NLRP3、caspase-1、gasdermin D的表达水平。结果与对照组相比,糖尿病组小鼠主动脉中eNOS含量明显升高(P＜0.05),焦亡相关信号蛋白NLRP3、caspase-1、gasdermin D的表达水平升高,经过apelin-13处理后,糖尿病小鼠血管壁eNOS含量进一步升高(P＜0.05),焦亡相关信号蛋白NLRP3、caspase-1、gasdermin D的表达水平也随之升高(P＜0.05),给予eNOS抑制剂L-NAME之后,糖尿病小鼠主动脉eNOS含量降低(P＜0.05),焦亡相关信号蛋白NLRP3、caspase-1、gasdermin D的表达水平也随之降低(P＜0.05)。结论 Apelin-13可能通过eNOS/NO途径促进糖尿病小鼠主动脉细胞焦亡相关蛋白的表达,导致糖尿病小鼠血管结构损伤和功能。

关键词: 糖尿病, 主动脉, apelin-13, 焦亡, eNOS

Abstract: Objective To observe the effects and mechanisms of Apelin-13 on expression of pyroptosis related proteins in aorta of diabetic mice. Methods C57/BL mice of eight weeks old were used as control group;kkAy mice of eight weeks old were used as type 2 diabetic models;osmotic pumps were used to treat kkAy mice with apelin-13 at a rate of 30 μg/(kg·d),and L-NAME(eNOS inhibitor) was injected intraperitoneally at a dose of 10 mg/(kg·d) to kkAy mice. Blood was collected for detection of Hb1Ac. The aortae were harvested and fixed. Morphological changes were observed with HE staining. Expression of eNOS,NLRP3,caspase-1 and gasdermin D were measured with immunohistochemical staining. Results Compared to the control group, the level of eNOS in the aorta of diabetic mice was significantly higher than that in control mice (P＜0.05),the levels of NLRP3,caspase-1 and gasdermin D were also higher than that in control mice. After apelin-13 treatment,the expressions of eNOS,NLRP3,caspase-1 and gasdermin D were further increased (P＜0.05). After L-NAME and apelin-13 treatment, the expressions of eNOS, NLRP3,caspase-1 and gasdermin D were reduced as compared to apelin-13 treatment alone(P＜0.05). Conclusions Apelin-13 may promote the expression of pyroptosis related protein in aortic cells by increasing eNOS/NO pathway,which would induce structural and functional damage in diabetic arteries.

Key words: diabetes, aorta, apelin-13, pyroptosis, eNOS

中图分类号:

R363

王炀佳, 张佳, 李宾, 曾翔俊. Apelin-13通过eNOS/NO促进糖尿病小鼠主动脉细胞焦亡相关蛋白的表达[J]. 基础医学与临床, 2020, 40(2): 155-160.

WANG Yang-jia, ZHANG Jia, LI Bin, ZENG Xiang-jun. Apelin-13 promotes expression of pyroptosis related protein in aortic cells in diabetic mice through eNOS/NO pathway[J]. Basic & Clinical Medicine, 2020, 40(2): 155-160.

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