线粒体ALDH2通过调控自噬对缺氧性肺动脉高压的保护机制研究  

Protective mechanism of mitochondrial ALDH2 on hypoxic pulmonary hypertension by regulating autophagy

作　　者：李小荣 鲜维 谭鑫 陈永锋[1] 唐碧[1] 张恒[1] 康品方[1] 王洪巨[1] LI Xiao-rong;XIAN Wei;TAN Xin;CHEN Yong-feng;TANG Bi;ZHANG Heng;KANG Pin-fang;WANG Hong-ju(Department of Cardiovascular Disease,The First Affiliated Hospital of Bengbu Medical College,Bengbu Anhui 233004;Key Laboratory of Basic and Clinical Cardiovascular and Cerebrovascular Diseases,Bengbu Medical College,Bengbu Anhui 233030,China)

机构地区：[1]蚌埠医学院第一附属医院心血管内科,安徽蚌埠233004 [2]蚌埠医学院心脑血管基础与临床转化实验室,安徽蚌埠233030

出　　处：《蚌埠医学院学报》2023年第1期66-71,共6页Journal of Bengbu Medical College

基　　金：国家自然科学基金面上项目(81970313);安徽省自然科学基金青年项目(1908085QH353);安徽省教育厅优秀人才基金(gxyq2020022);安徽省高校协同创新项目(GXXT-2020-019);蚌埠医学院研究生创新课题(byycx21066)。

摘　　要：目的:探讨激活线粒体乙醛脱氢酶2(ALDH2)可以降低因缺氧所引起的平滑肌细胞自噬,并降低肺动脉平滑肌细胞(PASMCs)的增殖,分析ALDH2对缺氧性肺动脉高压平滑肌增殖的调控关系。方法:将SPF级雄性SD大鼠分4组:正常对照组(N组)、常氧+ALDH2特异性激动剂Alda-1组(N+Alda-1组)、缺氧组(H组)、缺氧+Alda-1组(H+Alda-1组),将PASMCs分为6组:常氧组(N组)、常氧+Alda-1组(NA组)、缺氧组(H组)、缺氧+Alda-1组(HA组)、缺氧+ALDH2抑制剂Daidzin组(HD组)、缺氧+Alda-1+Daidzin组(HAD组)。HE染色观察各组动物肺组织中肺动脉病理变化;免疫荧光鉴定肺动脉平滑肌细胞;CCK-8测定各组细胞增殖能力;Annexin V-FITC/PI双染测定细胞凋亡水平;Western blotting检测各组ALDH2、p62、Beclin1、LC3B等蛋白的表达。结果:与N组相比,H组肺小动脉管壁增厚,管腔变窄;与HC组相比,H+Alda-1组的肺小动脉管壁厚度减轻,管腔狭窄程度有所改善;与N组相比,H组的ALDH2表达降低(P<0.05),自噬相关蛋白p62、Beclin1、LC3B均明显升高(P<0.01),细胞增殖明显增加(P<0.01);与H组相比,HA组ALDH2表达明显升高(P<0.01),自噬相关蛋白p62、Beclin1、LC3B均明显降低(P<0.01),细胞增殖受到明显抑制(P<0.01)。结论:线粒体ALDH2对缺氧诱导的PASMCs的增殖有着显著的抑制作用,其机制可能与ALDH2对细胞的自噬调节有关。Objective:To investigate the effect of activating mitochondrial aldehyde dehydrogenase on the autophagy of smooth muscle cells induced by hypoxia and the proliferation of pulmonary artery smooth muscle cells,and to analyze the regulation of mitochondrial aldehyde dehydrogenase on the proliferation of smooth muscle cells induced by hypoxia pulmonary arterial hypertension.Methods:Male SD rats of SPF grade were divided into four groups:normal control group(N group),normoxia+ALDH2 agonist Alda-1 group(N+Alda-1 group),model group(H group),and hypoxia+Alda-1 group(H+Alda-1 group).PASMCs was divided into six groups:normoxia group(N group),normoxia+Alda-1 group(NA group),hypoxia group(H group),hypoxia+Alda-1 group(HA group),hypoxia+ALDH2 inhibitor Daidzin group(HD group),and hypoxia+Alda-1+Daidzin group(HAD group).HE staining was performed to observe the pathological changes of pulmonary artery in the lung tissue of each group,immunofluorescence was used to identify pulmonary artery smooth muscle cells,CCK-8 was applied to determine the cell viability and proliferation of each group,Annexin V-FITC/PI double staining was employed to detect apoptosis level,and Western blotting was used to analyze the protein expression of ALDH2,p62,Beclin1 and LC3B.Results:Compared with the N group,the walls of pulmonary arterioles was thickened and the lumen was narrowed in the H group.Compared with the H group,the thickness of pulmonary small artery wall was reduced,and the degree of stenosis was improved in the H+Alda-1 group.Compared with the group N,the expression of ALDH2 decreased(P<0.05),the expression of autophagy-related proteins p62,Beclin1 and LC3B increased significantly(P<0.01),and the cell proliferation increased significantly in the group H(P<0.01).Compared with the group H,the expression of ALDH2 was significantly increased(P<0.01),the expression of autophagy-related proteins p62,Beclin1 and LC3B obviously decreased(P<0.01),and the cell proliferation was markedly inhibited in the HA group(P<0.01).Conclusions:Mitochondrial

关 键 词：肺动脉高压 线粒体乙醛脱氢酶 自噬 

分 类 号：R544[医药卫生—心血管疾病]