跨膜蛋白TMEM88在LPS/D-GaIN诱导的急性肝损伤中的作用  

Role of the transmembrane protein TMEM88 in acute liver injury induced by LPS/D-GaIN

作　　者：何翠霞 朱敏慧 徐媛媛 王雪枫 丁佳翔 周焕 HE Cuixia;ZHU Minhui;XU Yuanyuan;WANG Xuefeng;DING Jiaxiang;ZHOU Huan(Clinical Trials Center,the First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233004,China;不详)

机构地区：[1]蚌埠医科大学第一附属医院国家药物临床试验机构,安徽蚌埠233004 [2]蚌埠医科大学药学院,安徽蚌埠233030 [3]蚌埠医科大学公共基础学院,安徽蚌埠233030

出　　处：《中华全科医学》2024年第5期786-790,共5页Chinese Journal of General Practice

基　　金：蚌埠医科大学“512人才培育计划”优秀青年教师基金项目(by51201313)。

摘　　要：目的探讨脂多糖(LPS)联合D-半乳糖胺(D-GaIN)诱导急性肝损伤小鼠中TMEM88的表达变化,并研究TMEM88表达高低对LPS诱导的AML-12细胞炎症因子分泌的影响。方法体内,将20只小鼠按随机数字表法随机分为正常组与模型组,每组10只,模型组采用LPS/D-GaIN联合诱导,收集小鼠肝脏组织和血液。体外,AML-12细胞经LPS刺激及TMEM88转染,测定TMEM88及炎症因子的表达变化。结果模型组小鼠肝脏组织发生明显损伤,ALI模型造模成功率为80%。此外,模型组小鼠肝脏TMEM88表达水平均明显升高(P<0.05)。在AML-12细胞中,LPS刺激的最适条件为100 ng/mL,刺激24 h。pEGFP-C1-TMEM88和TMEM88-siRNA经验证成功转染进LPS刺激的AML-12细胞内(P<0.05)。此外,TMEM88过表达会导致炎症因子IL-1β、IL-6及TNF-α分泌上调(P<0.01),而敲低TMEM88则会减少炎症因子的分泌(P<0.05),以上实验结果表明TMEM88的表达水平可能影响炎症过程。结论TMEM88的表达水平在LPS/D-GaIN诱导的急性肝损伤模型中具有重要作用。Objective This study aims to investigate the changes of TMEM88 expression in mice with acute liver injury induced by lipopolysaccharide(LPS)combined with D-galactosamine(D-GaIN),and investigate the effect of high and low TMEM88 expression on the secretion of inflammatory factors in AML-12 cells induced by LPS.Methods In vivo,20 mice were randomly divided into normal and model groups with 10 mice in each group according to random number table method.The model group was induced by LPS/D-GaIN combination,and liver tissues and blood of mice were collected.In vitro,AML-12 cells were stimulated by LPS and transfected with TMEM88 to access the changes in the expression of TMEM88 and inflammatory factors.Results The model group exhibited significant liver tissue,with a successful ALI modelling rate of 80%.In addition,the hepatic TMEM88 expression level was significantly increased in the model group(P<0.05).In AML-12 cells,the optimal condition for LPS stimulation was determined to be 100 ng/mL for 24 h.pEGFP-C1-TMEM88 and TMEM88-siRNA were verified to be successfully transfected into LPS-stimulated AML-12 cells(P<0.05).Furthermore,overexpression of TMEM88 resulted in an upregulation of inflammatory factors IL-1β,IL-6,and TNF-α(P<0.01),while knockdown of TMEM88 reduced the secretion of inflammatory factors(P<0.05).These experimental results suggest that the expression level of TMEM88 may influence the inflammatory process.Conclusion The expression level of TMEM88 plays an important role in the LPS/D-GaIN-induced acute liver injury model.

关 键 词：TMEM88 LPS/D-GaIN 急性肝损伤 炎症因子 

分 类 号：R575[医药卫生—消化系统] R-332[医药卫生—内科学]