SIRT1通过降低NF-kB p65表达减轻异烟肼致人肝细胞损伤的研究  

SIRT1 protects human liver cells from Isoniazid-induced injury by decreasing expression of NF-kB p65

作　　者：张一杨 李莹淑 李金凤 李标 崇英之 郑国颖 孙淑丰 冯福民 Yi-yang Zhang;Ying-shu Li;Jin-feng Li;Biao Li;Ying-zhi Chong;Guo-ying Zheng;Shu-feng Sun;Fu-min Feng(School of Public Health(Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry),North China University of Science and Technology,Tangshan,Hebei 063000,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：《中国现代医学杂志》2018年第22期7-12,共6页China Journal of Modern Medicine

基　　金：河北省自然科学基金资助项目(No:H2016209300)

摘　　要：目的探讨沉默信息调节因子1(SIRT1)在异烟肼致人肝细胞损伤中的作用。方法培养人正常肝细胞HL-7702,实验分为6组:空白对照组、异烟肼组、异烟肼+SIRT1激动剂组、SIRT1激动剂对照组、异烟肼+SIRT1抑制剂组、SIRT1抑制剂对照组。取各组细胞上清液测定丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)含量;实时荧光定量聚合酶链反应(q RT-PCR)检测肝细胞SIRT1、NF-k B p65 mRNA表达水平;酶联免疫吸附法(ELISA)检测SIRT1、核转录因子k B(NF-k B p65)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)蛋白表达水平。结果与空白对照组比较,异烟肼组细胞SIRT1的mRNA和蛋白表达下降(P<0.05),其下游靶基因NF-k B p65的mRNA和蛋白表达升高(P<0.05),炎症因子IL-6、TNF-α蛋白表达水平升高(P<0.05)。加入SIRT1激动剂可减轻异烟肼引起的炎症反应,加入SIRT1抑制剂可使NF-k B p65、IL-6、TNF-α表达水平进一步升高从而加重细胞的炎症损伤。结论异烟肼诱导肝细胞损伤过程中,降低SIRT1水平,增加炎症因子的表达。SIRT1的激活可以通过降低NF-k B p65表达进而减轻肝细胞损伤的发生。Objective To investigate the effect of silent information regulator 1(SIRT1)on liver injury induced by Isoniazid(INH)in human normal liver cells HL-7702.Methods HL-7702 cells were cultured in RPMI 1640 supplemented with 10%FBS and divided into 6 groups including a control group,an INH group,an INH+SRT1720 group,a SRT1720 group,an INH+EX527 group and an EX527 group.The content of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in cell supernatant was determined.The expressions of SIRT1 and nuclear factor kappa B p65(NF-kB p65)mRNAs were analyzed by qRT-PCR.The concentrations of SIRT1 and NF-kB p65 proteins,interleukin 6(IL-6)and tumor necrosis factorα(TNF-α)were detected by ELISA.Results Compared with the control group,the expressions of SIRT1 at mRNA and protein levels were decreased(P<0.05),the expression levels of NF-kB p65 mRNA and protein were significantly increased(P<0.05),and the secretion of IL-6 and TNF-αalso increased(P<0.05)in the INH group.Adding SRT1720 could relieve the inflammatory reaction caused by INH.However,the expression levels of NF-kB p65,IL-6 and TNF-αwere significantly enhanced by a SIRT1 inhibitor EX527.Conclusions Isoniazid can bring out the liver injury,decrease the level of SIRT1 and increase the levels of inflammatory factors.The activation of SIRT1 can inhibit the expressions of NF-kB p65 and inflammatory factors,then reduce the occurrence of hepatocyte injury.

关 键 词：沉默信息调节因子1 NF-KBP65 异烟肼 肝损伤 

分 类 号：R575[医药卫生—消化系统]