细胞外HSP22在ox-LDL诱导冠状动脉内皮细胞炎症损伤中对 TLR4/NF-κB信号通路的影响  

Impact of extracellular HSP22 on TLR4/NF-κB signaling pathway in ox-LDL induced coronary artery endothelial cell inflammatory injury

作　　者：曾圣强 吴延庆[2] 杨柳[1] 徐玉琴 ZENG Shengqiang;WU Yanqing;YANG Liu;XU Yuqin(Department of Cardiovascular Medicine,Jiangxi Provincial People’s Hospital/First Affiliated Hospital of Nanchang Medical College,Nanchang,Jiangxi 330006,China;Department of Cardiovascular Internal Medicine,Second Affiliated Hospital of Nanchang University,Nanchang,Jiangxi 330006,China;Department of General Medicine,Nanchang Municipal Sixth Hospital,Nanchang,Jiangxi 330006,China)

机构地区：[1]江西省人民医院/南昌医学院第一附属医院心血管内科,南昌330006 [2]南昌大学第二附属医院心血管内科,南昌330006 [3]南昌市第六医院大内科,南昌330006

出　　处：《重庆医学》2025年第2期297-302,共6页Chongqing Medical Journal

基　　金：江西省卫生健康委员会科技计划项目(202210143)。

摘　　要：目的 探讨细胞外热休克蛋白(HSP)22在氧化-低密度脂蛋白(ox-LDL)诱导的冠状动脉内皮细胞(HCAECs)炎症损伤中对Toll样受体(TLR)4/核因子-κB(NF-κB)信号通路的影响。方法 通过体外培养HCAECs,予以ox-LDL预处理,建立高脂致内皮细胞损伤模型;外源性给予重组人HSP22(rhHSP22)处理,观察rhHSP22对内皮细胞白细胞介素(IL)-8、血管细胞黏附分子(VCAM)-1和NF-κB等炎症相关蛋白的表达及内皮细胞凋亡的影响。在TLR4抑制剂E5564作用下,研究HSP22与TLR4/NF-κB信号通路的关系。采用Western blot检测IL-8、VACM-1和NF-κB蛋白的表达情况,流式细胞术检测各组内皮细胞凋亡情况。结果 与CNT组比较,rhHSP22组、rhHSP22+ox-LDL组、rhHSP22+E5564组、rhHSP22+E5564+ox-LDL组IL-8、VACM-1、NF-κB蛋白相对表达水平升高,差异有统计学意义(P<0.05);与rhHSP22组比较,rhHSP22+ox-LDL组IL-8、VACM-1、NF-κB蛋白相对表达水平升高,差异有统计学意义(P<0.05);与rhHSP22+ox-LDL组比较,rhHSP22+E5564+ox-LDL组IL-8、VACM-1蛋白相对表达水平下降,差异有统计学意义(P<0.05)。与CNT组比较,rhHSP22组、rhHSP22+ox-LDL组、rhHSP22+E5564+ox-LDL组细胞凋亡率升高,差异有统计学意义(P<0.05);与rhHSP22组比较,rhHSP22+ox-LDL组细胞凋亡率升高,差异有统计学意义(P<0.05);与rhHSP22+ox-LDL组比较,rhHSP22+E5564+ox-LDL组细胞凋亡率下降,差异有统计学意义(P<0.05)。结论 在ox-LDL诱导的HCAECs炎症损伤中,细胞外HSP22通过激活TLR4/NF-κB信号通路诱导IL-8、VACM-1、NF-κB蛋白表达,促进内皮细胞凋亡。Objective To investigate the effect of extracellular heat shock protein(HSP)22 on Toll-like receptor(TLR)4/nuclear factor-κB(NF-κB)signaling pathway in oxidative-low-density lipoprotein(ox-LDL)-induced inflammatory damage in coronary endothelial cells(HCAECs).Methods HCAECs were cultured in vitro and pretreated with ox-LDL to establish a model of high-lipid-induced endothelial cell injury.Recombinant human HSP22(rhHSP22)was exogenously treated.The effects of rhHSP22 on the expression of inflammation-related proteins such as interleukin(IL)-8,vascular cell adhesion molecule(VCAM)-1 and NF-κB in endothelial cells and endothelial cell apoptosis were observed.The relationship between HSP22 and TLR4/NF-κB signaling pathway was investigated under the action of TLR4 inhibitor E5564.Western blot was used to detect the expression of IL-8,VACM-1 and NF-κB proteins,and flow cytometry was used to detect the apoptosis of endothelial cells in each group.Results Compared with the CNT group,the relative expression levels of IL-8,VACM-1 and NF-κB protein in the rhHSP22 group,rhHSP22+ox-LDL group,rhHSP22+E5564 group and rhHSP22+E5564+ox-LDL group were significantly increased,and the differences were statistically significant(P<0.05).Compared with the rhHSP22 group,the relative expression levels of IL-8,VACM-1 and NF-κB protein in the rhHSP22+ox-LDL group were significantly increased,and the differences were statistically significant(P<0.05).Compared with the rhHSP22+ox-LDL group,the relative expression levels of IL-8 and VACM-1 in the rhHSP22+E5564+ox-LDL group were decreased,and the differences were statistically significant(P<0.05).Compared with the CNT group,the apoptosis rate in the rhHSP22 group,rhHSP22+ox-LDL group and rhHSP22+E5564+ox-LDL group was significantly increased,and the difference was statistically significant(P<0.05).Compared with the rhHSP22 group,the apoptosis rate in the rhHSP22+ox-LDL group was increased,and the difference was statistically significant(P<0.05).Compared with the rhHSP22+ox-LDL group,the

关 键 词：热休克蛋白22 氧化-低密度脂蛋白 冠状动脉内皮细胞 炎症 Toll样受体4/核因子-κB 

分 类 号：R543.3[医药卫生—心血管疾病]