糖蛋白130在急性肝损伤中负性调控内质网应激作用及机制  

Study on the role and mechanism of gp130 negatively regulating endoplasmic reticulum stress in acute liver injury

作　　者：李霞 李映 何伟 邓洁 蒋小铃 姜金莲 蒋智钢 程其娇 刘霞 何毅怀 LI Xia;LI Ying;HE Wei;DENG Jie;JIANG Xiaoling;JIANG Jinliang;JIANG Zhigang;CHENG Qijiao;LIU Xia;HE Yihuai(Department of Infectious Diseases,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China;不详)

机构地区：[1]遵义医科大学附属医院感染科,贵州遵义563000 [2]遵义医科大学公共卫生学院,贵州遵义563099

出　　处：《实用医学杂志》2022年第12期1499-1505,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金(编号:81560110);贵州省科学技术基金项目(编号:黔科合平台人才[2017]5733-013);贵州省卫生健康委科学技术基金项目(编号:gzwjkj2020-1-041);遵义市科技计划项目(编号:遵市科合HZ字(2019)粤199号);遵义医学院硕士启动基金项目(编号:院字(2017)33号);遵义医学院附属医院硕士启动项目(编号:院字(2018)38号);遵义医科大学研究生科研基金(编号:ZYK035)。

摘　　要：目的探讨肝内糖蛋白130(glycoprotein 130,gp130)在急性肝损伤中表达的变化及其对肝细胞凋亡的影响及机制。方法首先通过四氯化碳(carbon tetrachloride,CCl4)诱导小鼠急性肝损伤,检测肝内gp130表达、内质网应激(endoplasmic reticulum stress,ERS;以Caspase-12标记)、细胞凋亡(以Cleaved caspase-3表达及TUNEL综合评估)的变化;其次通过4-苯基丁酸(4-phenylbutyric acid,PBA;ERS抑制剂)干预小鼠,探讨ERS对肝内gp130表达的影响;最后敲减模型小鼠肝内gp130表达,探讨gp130对肝损伤、肝细胞凋亡的影响及作用机制。结果模型小鼠肝内gp130表达上调,ERS及细胞凋亡信号显著激活(P<0.05);PBA减低肝内gp130表达,减轻肝细胞凋亡反应(P<0.05);肝内gp130的下调加重了CCl4诱导的小鼠肝损伤、ERS和肝细胞凋亡反应(P<0.05)。结论在急性肝损伤中ERS促进肝内gp130表达上调;gp130的上调有利于减轻肝损伤,机制可能与负性调控ERS介导的肝细胞凋亡有关。Objective To investigate the changes in the expression of intrahepatic glycoprotein 130(gp130)in acute liver injury and its effect on hepatocyte apoptosis and its mechanism.Method First,carbon tetrachloride(CCl4)was used to induce acute liver injury in mice to detect changes in the expression of gp130 in the liver,endoplasmic reticulum stress(ERS;labeled with caspase-12),and apoptosis(with cleaved caspase-3expression and TUNEL comprehensive evaluation);Secondly,4-phenylbutyric acid(PBA;ERS inhibitor)was used to intervene in mice to explore the effect of ERS on the expression of gp130 in the liver;Finally,the expression of gp130 in the liver of the model mice was knocked down,and the effect and mechanism of gp130 on liver injury and hepatocyte apoptosis were explored.Result The expression of gp130 in the liver of model mice is up-regulated,and ERS and apoptosis signals are significantly activated(P<0.05);PBA reduces the expression of gp130 in the liver and reduces the apoptotic response of hepatocytes(P<0.05);the down-regulation of gp130 aggravated the CCl4-induced liver injury,ERS,and hepatocyte apoptosis in mice(P<0.05).Conclusion ERS promotes the upregulation of gp130 expression in acute liver injury;up-regulation of gp130 is beneficial to alleviate liver injury,and the mechanism may be related to negative regulation of ERS-mediated hepatocyte apoptosis.

关 键 词：糖蛋白130 肝细胞凋亡 内质网应激 急性肝损伤 小鼠模型 

分 类 号：R575.3[医药卫生—消化系统]