MS-275对异烟肼致肝细胞损伤中内质网应激的影响  

Effect of MS-275 on endoplasmic reticulum stress during hepatocyte injury induced by isoniazid

作　　者：李金凤 杜莹 李标 张一杨 李莹淑 韩铁生 任琦 冯福民 LI Jin-feng;DU Ying;LI Biao;ZHANG Yi-yang;LI Ying-shu;HAN Tie-sheng;REN Qi;FENG Fu-min(School of Public Health,North China University of Science and Technology,Tangshan 063000,Hebei,China)

机构地区：[1]华北理工大学公共卫生学院,河北省煤矿卫生与安全重点实验室,河北唐山063000

出　　处：《广东医学》2018年第19期2874-2876,2880,共4页Guangdong Medical Journal

基　　金：河北省自然科学基金资助项目(编号:H2016209300)

摘　　要：目的探讨MS-275对异烟肼(INH)致肝细胞损伤过程中内质网应激(ERS)的影响。方法人正常肝细胞HL-7702接种于6孔板,预培养24 h,随机分为对照组、INH组(1 000μg/m L INH)、MS-275组(5μmol/L MS-275)、INH+MS-275组(1 000μg/m L INH+5μmol/L MS-275),共4个组,经不同药物处理6 h后,收获细胞。RT-PCR法检测HDAC1、GRP78和CHOP的mRNA水平,ELISA法检测HDAC1、GRP78和CHOP的蛋白含量,CCK8法检测细胞存活率。结果 INH处理6 h后肝细胞即出现损伤。给予组蛋白去乙酰化酶抑制剂MS-275后,细胞内ERS标志性分子GRP78的mRNA和蛋白水平显著增加(P <0. 05);而CHOP的mRNA和蛋白表达则显著下降(P <0. 05),且肝细胞存活率明显增加(P <0. 05)。结论INH致肝损伤过程中MS-275可以通过调控ERS缓解肝细胞损伤。Objective To investigate the effect of MS-275 on endoplasmic reticulum stress（ ERS） in liver injury induced by isoniazid（ INH）. Methods HL-7702 cells were inoculated,cultured for 24 h,and treated with MS-275 for 6 h. RT-PCR was used to detect the mRNA levels of HDAC1,GRP78 and CHOP. The protein contents of HDAC1,GRP78 and CHOP were detected by ELISA method. Results INH treatment induced hepatocyte injury. After the addition of the histone deacetylase inhibitor MS-275,the mRNA and protein levels of GRP78,the marker molecule of ERS,were significantly increased（ P〈0. 05）. At the same time,the mRNA and protein expression levels of CHOP were significantly reduced（ P〈0. 05）,and the survival rate of hepatocytes was significantly increased（ P〈0. 05）,suggesting that MS-275 may regulate ERS in the process of hepatocyte injury. Conclusion MS-275 may regulate ERS and alleviate hepatocytes injury in INH-induced liver injury.

关 键 词：异烟肼 MS-275 内质网应激 肝损伤 

分 类 号：R575[医药卫生—消化系统]