MAPK信号通路及内质网应激对心肌缺血再灌注损伤的影响  

Effects of MAPK Signaling Pathway and Endoplasmic Reticulum Stress on Myocardial Ischemia-Reperfusion Injury

作　　者：杨天睿[1,2] 叶堃 苗云波 段靳岚[1,2] 杨起江 张思思 YANG Tianrui;YE Kun;MIAO Yunbo;DUAN Jinlan;YANG Qijiang;ZHANG Sisi(Geriatric Department,The First People’s Hospital of Yunnan Province,Kunming 650032,China;The Affiliated Hospital of Kunming University of Science and Technology,Kunming 650032,China;Medical School,Kunming University of Science and Technology,Kunming 650500,China)

机构地区：[1]云南省第一人民医院老年病科,云南昆明650032 [2]昆明理工大学附属医院,云南昆明650032 [3]昆明理工大学医学院,云南昆明650500

出　　处：《昆明理工大学学报（自然科学版）》2022年第2期83-88,共6页Journal of Kunming University of Science and Technology(Natural Science)

基　　金：云南省基础研究计划(昆医联合专项)项目(2019FE001(-128));云南省老年疾病临床医学研究中心老年共病诊疗及临床转化研究项目(202102AA310069);云南省董碧蓉专家工作站项目(202105AF150032)。

摘　　要：从MAPK信号通路及内质网应激方面验证心肌缺血再灌注损伤机制.采用PowerLab型Langendorff离体心脏灌流系统建立实验树鼩心肌缺血再灌注模型.将40只树鼩随机分为3组,分别为空白对照组、缺血模型组和缺血再灌注模型组,并保证每组试验成功10只.将空白对照组持续灌注60 min,缺血模型组灌注稳定后停灌30 min,再灌注模型组,停灌30 min后复灌30 min,各组灌注液均为K-H溶液.灌注结束后,采用Tunel法检测细胞凋亡率,Western blot测定Bcl-2、Bax、P-P38、p-JNK-1、P-ERK、GRP78、CHOP-1蛋白表达量.缺血模型组、再灌注模型组的细胞凋亡率及BAX蛋白表达量升高明显,其中再灌注模型组最显著;凋亡蛋白BCL-2的相对表达量在再灌注组显著下调,缺血模型组次之,而在对照组表达量最高.相较于空白对照组及缺血模型组,再灌注模型组中磷酸化P38、JNK、ERK蛋白表达量最高,且内质网应激蛋白GRP78和CHOP-1表达量也显著升高,以上结果均具有统计学意义.细胞通过启动MAPK信号通路,激活内质网应激系统,加速细胞凋亡,引起心肌缺血再灌注损伤的发生及发展.This article aims to analyze the mechanism of myocardial ischemia-reperfusion injury from the perspective of MAPK signaling pathway and endoplasmic reticulum stress.A myocardial ischemia reperfusion model was established by Langendorff heart perfusion in vitro system with the experimental tree shrews.Forty tree shrews were randomly divided into 3 groups,namely control group,ischemia group and ischemia reperfusion(I/R)group,10 successful ones guaranteed in each group.The control group was continuously perfused for 60 minutes,the ischemia group stopped being perfused for 30 minutes after continuous perfusion and the I/R group resumed perfusion for 30 minutes after stopping perfusion.K-H solution was used in all groups.After perfusion,the apoptosis rates were detected by Tunel method and protein expression of Bcl-2,Bax,GRP78,CHOP-1,P-P38,P-JNK-1,P-ERK,GRP78 and CHOP-1 were determined by Western blot.The apoptosis rate and the protein expression of Bax were increased both in ischemia group and I/R group,especially in I/R group.Compared with control group and ischemia group,phosphorylated expression of P38,JNK,ERK evidently increased in I/R group,and the expression of GRP78 and CHOP-1 distinctly increased as well.All the above results were of statistical significance.Cells launch MAPK signaling pathway,activate endoplasmic reticulum stress,accelerate cell apoptosis and cause the occurrence and development of myocardial ischemia-reperfusion injury.

关 键 词：MAPK信号通路 心血管疾病 内质网应激 细胞凋亡 心肌缺血再灌注损伤 

分 类 号：R54[医药卫生—心血管疾病]