HSP60通过上调TREM2表达改善肺缺血再灌注损伤  

HSP60 attenuates lung ischemia-reperfusion injury by upregulating TREM2 expression

作　　者：梁芳特 刘豪 何小静 刘春霞 伍思怡 覃伊 潘灵辉[1] 林飞[1] Liang Fangte;Liu Hao;He Xiaojing;Liu ChunXia;Wu Siyi;Qin Yi;Pan Linhui;Lin Fei(Department of Anesthesiology,The Affiliated Tumor Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学附属肿瘤医院麻醉科,南宁530021

出　　处：《广西医科大学学报》2021年第5期877-881,共5页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81960022);广西自然科学基金面上项目(No.2020GXNSFAA159123);广西高等学校千名中青年骨干教师培育计划项目(No.2017-53);广西医学高层次骨干人才“139”计划培养项目(No.G201903011)。

摘　　要：目的:探讨热休克蛋白60(HSP60)调控2型髓系细胞触发受体(TREM2)对肺缺血再灌注损伤(LIRI)小鼠的保护作用。方法:将24只C57BL/6小鼠随机分成对照组、HSP60组、LIRI组、LIRI+HSP60组,每组6只。LIRI+HSP60组于术前1 h腹腔注射HSP60(5μg/g)。HSP60组腹腔注射等剂量的HSP60;对照组不做任何处理。LIRI组和LIRI+HSP60组小鼠建立LIRI模型,术后6 h收集左肺组织标本,苏木精-伊红(HE)染色法观察肺组织病理学变化,透视电镜观察肺组织超微结构改变,酶联免疫吸附法(ELISA)检测肺组织中炎性因子白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)的表达,实时荧光定量PCR(qPCR)法与Western blotting检测TREM2 mRNA及TREM2蛋白的相对表达水平。结果:与对照组和HSP60组比较,LIRI组肺组织损伤严重,肺组织结构改变明显,肺损伤评分明显增加(P<0.05),炎症因子IL-1β和IL-18水平均明显升高(均P<0.05),TREM2 mRNA及其蛋白相对表达水平均明显降低(均P<0.05)。与LIRI组比较,LIRI+HSP60组肺组织病理学损伤明显改善,肺损伤评分明显降低(P<0.05),炎症因子IL-1β和IL-18表达明显减少(均P<0.05),TREM2 mRNA及其蛋白的相对表达水平均明显升高(均P<0.05)。与对照组相比较,HSP60组TREM2 mRNA及蛋白的相对表达水平均明显升高(P<0.05)。结论:HSP60可以减轻LIRI,其机制可能与上调TREM2的表达有关。Objective:To study the protective effect of heat shock protein 60(HSP60)on regulatingtype 2 myeloid cell triggering receptor(TREM2)in lung ischemia/reperfusion injury(LIRI)in mice.Methods:Twenty-four healthy male SPF C57BL/6 mice were randomly divided into 4 groups(n=6):Control group,HSP60 group,LIRI group and LIRI+HSP60 group.The model of LIRI was established by clamping the left hilum with microvascular clamp.Hematoxylin-eosin(HE)staining was used to evaluate the lung injury.The ultrastructural changes of lung tissue were observed by transmission electron microscope.Enzyme-linked immune sorbent assay(ELISA)was used to measure the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18).The mRNA expression of TREM2 was measured by qPCR.The protein expression of TREM2 was measured by western blotting.Results:Compared with the control group and HSP60 group,the lung tissue injury was serious in LIRI group,the lung structure was changed obviously,lung injury score and the levels of IL-1βand IL-18 were significantly increased,and the mRNA and protein expression of TREM2 was decreased(P<0.05).Compared with LIRI group,LIRI+HSP60 group reversed the lung injury,decreased lung injury score and the levels of IL-1βand IL-18,and increased the mRNA and protein expression of TREM2(P<0.05).The mRNA and protein expression of TREM2 was also increased in HSP60 group when compared with the control group(P<0.05).Conclusion:HSP60 could alleviate LIRI and the mechanism might be related to activation of TREM2 expression.

关 键 词：HSP60 肺缺血再灌注损伤 TREM2 炎症反应 

分 类 号：R543[医药卫生—心血管疾病]