摘要
目的:探讨内质网应激(ERS)在慢性缺氧诱导的心肌细胞线粒体损伤中的作用及机制。方法:将8周龄雄性Wistar大鼠随机分为缺氧组、干预组和对照组,缺氧组和干预组大鼠在常压间歇缺氧环境中喂养,干预组同时给予ERS抑制剂4-PBA灌胃处理,对照组大鼠在空气中喂养。21 d后处死大鼠,游离心脏各组分并称重,取右心室组织制作超薄切片于透射电镜下观察线粒体形态。提取右心室组织线粒体用于JC-1荧光探针检测线粒体膜电位和比色法测定琥珀酸脱氢酶(SDH)及细胞色素C氧化酶(COX)活性。采用Western blotting方法检测右心室心肌组织中ERS标志性分子葡萄糖调节蛋白78(GRP78)及CCAAT/增强子结合蛋白同源蛋白(CHOP)表达水平。结果:缺氧组大鼠出现右心室肥大表现,电镜下观察到心肌细胞线粒体出现肿胀、嵴排列紊乱和膜完整性破坏等异常,同时,线粒体膜电位、COX及SDH活性均降低,CHOP及GRP78表达水平上调(P<0.05)。与缺氧组相比,干预组大鼠CHOP及GRP78表达水平下调,线粒体膜电位、COX及SDH活性均升高,线粒体结构异常得到部分缓解,右心室肥大有所改善(P<0.05)。结论:心肌细胞ERS介导的线粒体损伤参与慢性肺源性心脏病的发病过程,以ERS为靶点的心脏保护治疗可能成为慢性肺源性心脏病的潜在治疗策略。
Objective:To investigate the role of endoplasmic reticulum stress-mediated myocardial mitochondrial injury in the pathogenesis of chronic cor pulmonale.Methods:The 8-week-old male wistar Rats were randomly divided into hypoxia group,intervention group and control group.The rats in hypoxia group and intervention group were fed in atmospheric intermittent hypoxia environment.The rats in intervention group were treated with 4-PBA by gavage at the same time,and the rats in control group were fed in the air.After 21 days,the rats were killed and the cardiac components were separated and weighed.And then the morphology of mitochondria in the right ventricular was observed under transmission electron microscope.The mitochondria was extracted from the right ventricular tissue to detect the level mitochondrial membrane potential and the activities of succinate dehydrogenase(SDH)and cytochrome c oxidase(COX).Finally,the expression levels of glucose regulated protein 78(GRP78)and CCAAT/enhancer binding protein homologous protein(CHOP)were detected by Western blot.Results:The hypertrophy of the right ventricular was observed in the rats of hypoxia group,accompanied by mitochondrial abnormalities.Meanwhile,the mitochondrial membrane potential,COX and SDH activities were significantly reduced,and the expression levels of CHOP and GRP78 were up-regulated in the rats of hypoxia group(P<0.05).Compared with the hypoxia group,the expression levels of CHOP and GRP78 were downregulated,the mitochondrial membrane potential and the activities of COX and SDH were significantly increased,the mitochondrial abnormalities were partially alleviated,and the right ventricular hypertrophy was also relieved in the intervention group(P<0.05).Conclusion:The myocardial mitochondrial injury mediated by endoplasmic reticulum stress may be involved in the pathogenesis of chronic cor pulmonale.Cardioprotective drug targeting endoplasmic reticulum stress may become a potential therapy for chronic cor pulmonale.
作者
单虎
张蓉
张秋红
杨侠
高锦
张洁
李雅莉
张明
Shan Hu;Zhang Rong;Zhang Qiuhong;Yang Xia;Gao Jin;Zhang Jie;Li Yali;Zhang Ming(Department of Respiratory and Critical Care Medicine,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,710004;Department of Gastroenterology,The Shaanxi Provincial People’s Hospital,Xi’an,710068,China)
出处
《广西医科大学学报》
CAS
2022年第7期1061-1066,共6页
Journal of Guangxi Medical University
基金
国家自然科学基金项目(No.81700328)
陕西省创新能力支撑计划资助(No.2019KJXX-045)
西安交通大学第二附属医院科研基金[No.2020YJ(ZYTS)077、RC(GG)202003]。
关键词
内质网应激
线粒体
心肌细胞
肺心病
endoplasmic reticulum stress
mitochondrion
cardiomyocyte
cor pulmonale
