干预GLP-1通路保护过氧化氢诱导心肌细胞凋亡的研究  

Improvement of Cardiomyocyte Apoptosis Induced by Hydrogen Peroxide via the Intervention of GLP-1 Signal Pathway

作　　者：赵树梅[1] 张谦[1] 郭春艳[1] 

机构地区：[1]首都医科大学附属北京友谊医院心血管内科,100050

出　　处：《医学研究杂志》2017年第3期98-101,共4页Journal of Medical Research

基　　金：首都医科大学基础-临床科研基金资助项目(13-JL58)

摘　　要：目的观察Exendin-4(Ex-4,GLP-1受体激动剂)对H_2O_2孵育的心肌细胞凋亡的影响,探讨GLP-1通路干预心肌细胞损伤的机制。方法分离、培养心室肌细胞,分成5组:A组为对照组;B组为H_2O_2干预组(100μmol/L,24h);C组为H_2O_2+Ex-4(Ex-10nmol/L,孵育24h)组;D组为H_2O_2+Ex-4(Ex-20nmol/L,孵育24h)组;E组为H_2O_2+Ex-4+LY294002(Ex-20nmol/L,LY-5μmol/L,孵育24h)组。荧光染色测定各组细胞内活性氧簇(ROS)生成的水平;流式细胞仪测定各组细胞凋亡率情况。以Western blot法测定各组细胞凋亡蛋白及机制蛋白(PI_3K/AKT)的表达。结果与H_2O_2孵育组相比,Ex-4干预使得心肌细胞内ROS水平下降,细胞凋亡率下降,在高剂量组(D组)均达到差异统计学意义(P<0.05)。同时,Ex-4干预可使p-AKT/AKT表达显著增加,caspase-3表达显著下降(P<0.05);而这些效应可被LY294002共孵育(E组)所逆转。结论干预GLP-1通路,可缓解H_2O_2诱导的心肌细胞凋亡,此效应至少部分是通过影响PI_3K/AKT途径实现的。Objective To observe the effect of Exendin -4 on the apoptosis of cardiomyocyte induced by H2O2 , and approach the relationship between GLP - 1 signal pathway and the injury of cardiomyocyte. Methods Cardiomyocytes were isolated and cultured, and were divided into 5 groups. Intercelluar ROS （reactive oxygen species） was measured, and cell apoptosis rate was evaluated by Flow eytometry in different groups. Also expressions of apoptosis - associated proteins （ caspase - 3 ） and PI3 K/AKT were evaluated by western blot. Results Compared with H2O2 group, Ex - 4 co - incubation decreased the production of intercelluar ROS levels, also improved the cardiomyoeyte apoptosis. At the same time, Ex - 4 resulted in the alterations in expressions of the caspase - 3 and p - AKT/AKT proteins. However, these effects of Exendin - 4 were counteracted significantly by the co - incubation of LY294002. Conclusion The interventions of GLP - 1 signal pathway can improve cardiomyocyte apoptosis induced by H2O2 incubation, and the mechanisms might partly attribute to the PI3 K/AKT system.

关 键 词：GLP-1通路 氧化应激 心肌细胞凋亡 PI3K/AKT 

分 类 号：R3[医药卫生—基础医学]