白藜芦醇在缺氧/复氧诱导的肝细胞损伤中的保护作用及与TLR4/NF-κB通路的关系  

Resveratrol protects hepatocytes against hypoxia/reoxygenation injury and its relationship with TLR4/NF-κB pathway

作　　者：何雕[1] 张国庆[1] 郑道峰 魏续福[1] 刘锐[1] 吴忠均[1] 

机构地区：[1]重庆医科大学附属第一医院肝胆外科,重庆400016

出　　处：《第三军医大学学报》2016年第12期1398-1403,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81171562);重庆市科委科技人才培养计划(CSTC2013kjrc-qnrc10006)~~

摘　　要：目的探讨白藜芦醇(resveratrol,RES)在缺氧/复氧(hypoxia reoxygenation,H/R)诱导的大鼠肝细胞损伤中的保护作用及其相关分子机制。方法建立BRL-3A细胞(大鼠肝细胞株)H/R模型。建模前分别用RES和TLR4抑制剂(HTA125)预处理细胞。建模完成后,检测细胞存活率及细胞凋亡,观察细胞形态变化,检测细胞培养液中谷丙转氨酶(alanine transaminase,ALT)及炎症因子含量,检测细胞TLR4、NF-κB p65基因mRNA及蛋白水平表达及NF-κB p65入核情况。结果 H/R条件使细胞存活率明显降低,细胞凋亡率增加(P<0.01),受损细胞明显增多,ALT、IL-1β含量增多(P<0.01),TLR4和NF-κB p65表达水平显著提高(P<0.01),p65入核细胞比例提高(P<0.01)。经RES及HTA125预处理后,细胞存活率显著提高,细胞凋亡比例显著缩小(P<0.01),受损细胞减少,ALT、IL-1β含量降低(P<0.01),TLR4和NF-κB p65表达水平明显降低(P<0.01),p65入核细胞比例下降(P<0.01)。结论 RES可以减轻H/R诱导的BRL-3A肝细胞损伤,该作用可能与抑制TLR4/NF-κB信号通路有关。Objective To determine the protective effect of resveratrol（ RES） on hepatocytes induced by hypoxia / reoxygenation（ H / R） and investigate the molecular mechanism. Methods Before H / R model was established,BRL-3A cells were treated with RES or HTA125（ TLR4 inhibitor）. Survival rate and apoptosis were detected in the cells. Alanine transaminase（ ALT） and interleukin-1β（ IL-1β） in the culture were determined. The mRNA and protein expression levels of TLR4 and NF-κB p65 in the cells were determined by quantitative real-time PCR and Western blotting. Results H / R stimulation decreased cell survival rate and enhanced the apoptosis（ P 0. 01）. The expression levels of ALT and IL-1β were enhanced significantly（ P 0. 01）,and the expression levels of TLR4 and NF-κB p65 were markedly increased（ P 0. 01）. After pretreatment with RES or HTA125,the cell survival rate was increased（ P 0. 01） while the apoptosis decreased（ P 0. 01）. ALT and IL-1β were reduced significantly（ P 0. 01）,and the expression levels of TLR4 and NF-κB p65 were decreased（ P 0. 01）. Moreover,RES inhibited the translocation of NF-κB p65 after H / R stimulation in BRL-3A cells（ P 0. 01）. Conclusion RES can alleviate the hepatocyte injury induced by H / R,which may be related with inhibition of TLR4 / NF-κB signaling pathway.

关 键 词：白藜芦醇 缺氧/复氧 肝细胞损伤 Toll样受体4 核因子-ΚB 

分 类 号：R285.5[医药卫生—中药学] R322.47[医药卫生—中医学]