艾塞那肽对高糖培养心肌细胞的保护作用及机制  

Protective effects and mechanism of exenatide on H9C2 cardiomyocytes cultured with highglucose

作　　者：袁瑞霞[1] 郭志新[1] 景晓锐 刘佳[1] 黄艳[1] 

机构地区：[1]山西医科大学第二医院内分泌科,太原030001

出　　处：《中华糖尿病杂志》2016年第10期623-628,共6页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：山西省留学回国人员科技活动择优资助项目（2012年度）;山西省回国留学人员科研资助项目（2011-048）

摘　　要：目的观察胰高血糖素样肽I（GLP-1）受体激动剂艾塞那肽对高糖培养心肌细胞脂联素及其受体1（AdipoRl）、氧化应激及内质网应激的影响，探讨艾塞那肽对心肌细胞的保护作用及机制。方法取H9C2心肌细胞随机分为4组（每组n=3）：对照组（A组，5．6mmol／L糖培养基）、高糖组（B组，25.5mmol／L糖培养基）；高糖＋10nmol／L艾塞那肽组（C组）；高糖＋100nmol／L艾塞那肽组（D组）。按分组处理24h后，测定心肌细胞脂联素、AdipoRl、烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚单位相对分子质量22000的多肽（p22phox）、核因子E2相关因子2（Nrf2）和CCAAT／±曾强子结合蛋白（CHOP）表达。组间比较采用单因素方差分析，两两比较采用LSD-t检验。结果（1）与A组比较，B组心肌细胞脂联素、AdipoRl蛋白表达和Nrf2mRNA表达水平均显著降低（760±145比1490±168；0．59±0．08比0．91±O．07；0．56±0．02比1．00±O．00；t=7．942、6．922、10．689，均P〈0．05），而p22phox蛋白表达和CHOPmRNA表达水平升高（0．87＋0．02比0．56＋0．09；1．58±0．16比1．00±0．00；t=7．591、5．994，均P〈0．05）。（2）C组心肌细胞脂联素、AdipoRl蛋白和Nrf2mRNA水平分别为1070±142、0．69±0．02、0．71±0．09，高于B组（t=3．372、2．263、3．633，均P〈0．05）；而p22phox蛋白（0．66±0．04）和CHOPmRNA表达（1．26±0．28）低于B组，（声4．716、3．272，均P〈0．05）。（3）D组心肌细胞脂联素（1306±178）、AdipoRl蛋白（0．82±0．09）和Nrf2rnRNA水平f0．91±0．11）高于C组（t=2．575、2．349、4．792，均P〈0．05），而CHOPmRNA表达（0．96±O．09）低于C组（t=3．185，P〈0．05）。结论艾塞那肽可能通过调节脂联素及其介导的信号通路，减轻氧化应激和内质网应激对心肌细胞的损伤，对高糖培养的心肌细胞产生保护作用。Objective To explore the effect and underlying mechanism of exenatide on the eardiomyocytes through evaluating its impact on adiponectin and its receptors（AdipoR）, oxidative stress and endoplasmic reticulum stress in cardiomyocytes cultured with high glucose. Methods H9C2 cardiomyoeytes were randomly divided into following four groups （n=3）： group A： cardiomyoeytes were cultured in normal glucose concentration （5.6 mmol/L）; group B： cardiomyocytes were cultured in high glucose concentration （25.5 mmol/L）; group C： cardiomyocytes were cultured in high glucose concentration and 10 nmol/L GLP-1; group D： cardiornyocytes were cultured in high glucose concentration and 100 nmol/L GLP-1. Four groups were continued to be cultured for 24 h. The expression of adiponectin, AdipoR1, nicotinamide adenine dinucleotide （NADPH） oxidase subunit （p22phox） nuclear factor E2-related factor2 （Nrf2）, and C/EBP homologous protein（CHOP） were analyzed. Differences among groups were compared by one-way analysis of variance, pairwise comparison were conducted using LSD-t test. Results （1）The level of adiponeetin, the protein expression of AdipoR1, and the mRNA expression of Nrf2 were significantly decreased in group B than those in group A （760±145 vs 1 490±168; 0.59±0.08 vs 0.91±0.07; 0.56±0.02 vs 1.00 ± 0.00, t= 7.942, 6.922, 10.689; all P〈O.05）. The protein expression of p22phox, and the mRNA expression of CHOP were significantly increased in group B than those in group A（0.87±0.02 vs 0.56±0.09; 1.58± 0.16 vs 1.00±0.00; t=7.591, 5.994; all P〈0.05）. （2）The levels of adiponectin, AdipoR1 protein expression and the Nrf2 mRNA expression of group C（1 070±142, 0.69±0.02, 0.71±0.09） were significantly higher than those of group B（t=3.372, 2.263, 3.633; all P〈0.05）. The p22phox protein （0.66±0.04）and CHOP mRNA （1.26±0.28） of group C were markedly lower than those of group B（t=4.716, 3.272, all P〈 0.05）. （3）The level of adiponectin（1 306±

关 键 词：胰高血糖素样肽1 脂联素 肌细胞 心脏 氧化应激 内质网应激 高糖 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]