HMGB1和LPS导致普通及TLR4基因敲除小鼠肝组织损伤的研究  

The difference of TLR4 knock-out and common mice liver injury induced by HMGB1 or LPS

作　　者：黄绍芳[1] 吴飞[1] 朱难兰[1] 贺永文[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院感染科,湖北武汉430022

出　　处：《胃肠病学和肝病学杂志》2013年第10期1023-1025,共3页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的探索HMGB1与LPS导致普通及TLR4基因敲除小鼠肝组织损伤的差异,明确TLR4受体敲除对于HMGB1与LPS在致肝组织损伤中的影响。方法 HMGB1腹腔注射至普通小鼠和TLR4基因敲除小鼠,以D-氨基半乳糖胺(D-Galn)和脂多糖(LPS)制备急性肝衰竭模型小鼠作为对照组,用不同方法检测肝组织中HMGB1、HMGB1-mRNA的表达、血清中谷丙转氨酶(ALT)和HMGB1的含量。结果在普通小鼠,HE染色示对照组与实验组各个时间点均出现不同程度肝组织损伤,两组表现相似。两组免疫组化检测HMGB1表达随时间延长而增多,两组HMGB1-mRNA表达随时间延长而增高。在TLR4基因敲除小鼠,HE染色示对照组全程与空白组一样未出现肝损伤,免疫组化检测HMGB1和RT-PCR检测HMGB1-mRNA全程均无明显表达;实验组全程均出现不同程度肝组织损伤,HMGB1表达随时间延长而增多,HMGB1-mRNA表达随时间延长而增高。结论 HMGB1造成小鼠肝损伤及肝衰竭与TLR4信号途经关系不大,可能主要通过RAGE受体通路起作用;而LPS主要通过TLR4途经导致肝损伤。Objective To investigate the difference of TLR4 knock-out and common mice liver injury induced by HMGB1 or LPS. Methods HMGB1 or D-galaetosamine and lipopolysaccharide were intraperitoneally injected into TLR4 knock-out mice and normal mice, the expression of HMGB1 in liver tissues was detected by immunohistochemisty and RT-PCR, and the serum ALT and HMGB1 were quantified by ELISA. Results There were similar liver injury in the control group and the experimental group at each time point in common mice; there was no liver damage in the con- trol group at each time point, but liver injury in the experimental group in TLR4 knock-out mice. Conclusion Liver failure can also induced by HMGB1. The process of liver injury induced by HMGB1 was mainly associate with RAGE pathway. Liver damage induced by LPS can not happen without TLR4 receptor.

关 键 词：重组高迁移率族蛋白B1 脂多糖 肝衰竭 TLR4基因敲除小鼠 

分 类 号：R575[医药卫生—消化系统]