p38-MAPK介导AT2R对低氧/复氧损伤后PC12细胞的保护作用研究  

Study on AT2R protecting PC12 cells from hypoxia/reoxygenation injury mediated by p38-MAPK

作　　者：罗敏 刘雅婷 龙双涟 彭凤玲 LUO Min;LIU Yating;LONG Shuanglian;PENG Fengling(Department of Anesthesiology,the Second Affiliated Hospital,University of South China,Hengyang,Hunan 421001,China;Department of Histology and Embryology,Clinical Anatomy & Reproductive Medicine Application Institute,University of South China,Hengyang,Hunan 421001,China;2017 Grade Excellent Doctor Class,Hengyang Medical School,University of South,Hengyang,Hunan 421001,China;Department of Internal Medicine-Neurology,the Frist Affiliated Hospital,University of South China,Hengyang,Hunan 421001,China)

机构地区：[1]南华大学附属第二医院麻醉科,湖南衡阳421001 [2]南华大学衡阳医学院应用解剖与生殖医学研究所组织学与胚胎学教研室,湖南衡阳421001 [3]南华大学衡阳医学院,湖南衡阳421001 [4]南华大学附属第一医院神经内科,湖南衡阳421001

出　　处：《重庆医学》2021年第4期557-562,共6页Chongqing medicine

基　　金：应用解剖与生殖医学湖南省衡阳市重点实验室建设资助项目(2017KJ182)。

摘　　要：目的探讨p38-丝裂原活化蛋白激酶(MAPK)在血管紧张素Ⅱ2型受体(AT2R)活化影响缺氧/复氧(H/R)损伤大鼠肾上腺嗜铬细胞瘤(PC12)细胞存活中的作用。方法以连二亚硫酸钠(Na2S2O4)模拟细胞缺氧反应的环境,复制H/R损伤细胞模型(对照组),给予AT2R激动剂(CGP42112,CGP42112组)、p38-MAPK抑制剂(SB203580,SB203580组)和(或)AT2R抑制剂(PD123319)分别处理细胞,四氮唑盐(MTT)法检测细胞存活率,逆转录-聚合酶链式反应(RT-PCR)检测Bax和Bcl-2 mRNA表达,Western blot检测磷酸化p38-MAPK(p-p38-MAPK)、Bax和Bcl-2蛋白表达。结果与对照组比较,CGP42112组和SB203580组PC12细胞存活率升高(P<0.05)。CGP42112可下调细胞中p-p38-MAPK蛋白表达,PD123319可上调p-p38-MAPK蛋白表达,且均呈浓度和时间依赖性(P<0.05)。CGP42112组和SB203580组Bax mRNA及蛋白表达水平降低,Bcl-2 mRNA及蛋白表达水平升高(P<0.05)。结论AT2R活化可通过调控p38-MAPK信号通路而影响Bcl-2和Bax的表达,促进H/R损伤PC12细胞的存活。Objective To investigate the effect of p38-mitogen-activated protein kinase(MAPK)on the activation of angiotensinⅡtype 2 receptor(AT2R)in the survival of rat adrenal pheochromocytoma(PC12)cells damaged by hypoxia/reoxygenation(H/R).Methods Sodium dithionite(Na2S2O4)was used to simulate the environment of cellular hypoxia response to replicate the H/R injury cell model(the control group),AT2R agonist(CGP42112,the CGP42112 group)p38-MAPK inhibitor(SB203580,the SB203580 group)and(or)AT2R inhibitor(PD123319)was used to treat cells separately,MTT method was used to detect cell viability,reverse transcription-polymerase chain reaction(RT-PCR)was used to detect Bax and Bcl-2 mRNA expression,Western blot was used to detect phosphorylated p38-MAPK(p-p38-MAPK),Bax And Bcl-2 protein expression.Results Compared with the control group,the survival rate of PC12 cells in the CGP42112 group and the SB203580 group increased(P<0.05).CGP42112 could down-regulate the expression of p-p38-MAPK protein,and PD123319 could up-regulate the expression of p-p38-MAPK protein,with a concentration and time-dependent manner(P<0.05).The expression levels of Bax mRNA and protein in the CGP42112 group and the SB203580 group decreased,while the expression levels of Bcl-2 mRNA and protein increased(P<0.05).Conclusion AT2R activation can affect the expression of Bcl-2 and Bax by regulating the p38-MAPK signaling pathway,and promote the survival of PC12 cells damaged by H/R.

关 键 词：受体 血管紧张素 2型 血管紧张素Ⅱ2型受体拮抗剂 PC12细胞 缺氧/复氧损伤 P38丝裂原活化蛋白激酶类 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]