激活自噬改善炎性因子诱导的血管细胞粘附分子1的表达  

Effect of autophagy on inflammatory factors-induced vascular cell adhesion molecule 1 expression

作　　者：朱翔鸿 丁秦超 赖尚磊 殷玉杰 窦晓兵[1,2] 李松涛 ZHU Xiang-hong;DING Qin-chao;LAI Shang-lei;YIN Yu-jie;DOU Xiao-bing;LI Song-tao(College of Life Sciences,Zhejiang University of Traditional Chinese Medicine,Hangzhou,Zhejiang 310053,China)

机构地区：[1]浙江中医药大学生命科学学院,浙江杭州310053 [2]浙江中医药大学分子医学研究所,浙江杭州310053 [3]浙江中医药大学滨江学院,浙江杭州310053

出　　处：《现代预防医学》2019年第13期2419-2423,共5页Modern Preventive Medicine

基　　金：国家自然科学基金(81773422,81573132);浙江省医药卫生科技计划项目(2019310630);国家级大学生创新创业训练计划项目(201810344016);浙江省大学生科技创新活动计划暨新苗人才计划(2018R410010);黑龙江省教育部留学回国人员科研启动基金资助项目

摘　　要：目的血管细胞粘附分子(VCAM)1表达是心血管疾病发生的风险因素。本研究旨在揭示自噬对炎性因子诱导的VCAM-1表达的影响及潜在分子机制。方法以人原代脐静脉血管内皮细胞为研究对象,分别采用炎性因子(肿瘤坏死因子-α,TNF-α或白细胞介素-1β,IL-1β)、自噬激动剂雷帕霉素、自噬抑制剂氯喹等对细胞进行干预,检测VCAM-1的mRNA、蛋白表达及磷酸化ERK1/2MAPK的变化。结果炎性因子显著激活VCAM-1的转录及蛋白表达(P<0.05)。激活自噬可显著降低TNF-α诱导的VCAM-1表达,而抑制自噬显著加重TNF-α诱导的VCAM-1增加。ERK1/2MAPK抑制剂U0126显著抑制TNF-α诱导的VCAM-1表达(P<0.05)。自噬调控显著影响TNF-α诱导的磷酸化ERK1/2表达增加(P<0.05)。结论自噬激活可能通过ERK1/2MAPK参与的信号通路改善炎性因子诱导的VCAM-1表达增加,自噬调控可作为改善血管内皮细胞功能及其相关心血管疾病的潜在治疗手段。Objective To reveal the effect of autophagy on vcam-1 expression induced by inflammatory factors and its potential molecular mechanism.Methods Primary umbilical vein endothelial cells were studied,and inflammatory factors(tumor necrosis factor-alpha,TNF-α,or interleukin-1 beta,IL-1β),autophagy agonist rapamycin,and autophagy inhibitor chloroquine were used to detect the changes of VCAM-1 mRNA,protein expression and phosphorylation of ERK1/2 MAPK.Results Inflammatory factors significantly activated VCAM-1 transcriptional and protein expression(P<0.05).Activation of autophagy significantly decreased TNF-αinduced VCAM-1 expression,while inhibition of autophagy significantly increased TNF-αinduced VCAM-1 expression.The expression of VCAM-1 induced by TNF-αwas significantly inhibited by the ERK1/2 MAPK inhibitor U0126(P<0.05).Autophagy regulation significantly affected TNF-αinduced phosphorylation of ERK1/2(P<0.05).Conclusion Autophagy activation may improve the expression of VCAM-1-induced by inflammatory factors through a ERK1/2 MAPK involved pathway,and the regulation of autophagy can be used as a potential therapeutic approach to improve vascular endothelial cells dysfunction and further cardiovascular diseases.

关 键 词：自噬 炎性因子 血管细胞粘附分子1 血管内皮细胞 

分 类 号：R113[医药卫生—公共卫生与预防医学]