文献类型：期刊文献

中文题名：Toll样受体4在D-氨基半乳糖/内毒素介导的急性肝损伤中的表达

英文题名：The expression of toll-like receptor 4 in the endotoxin-induced acute hepatic injury

作者：晏春根[1];谢青[1];周霞秋[1];徐玉敏[1];俞红[1];郭清[1]

机构：[1]上海第二医科大学附属瑞金医院感染科,绍兴文理学院医学院200025

年份：2004

卷号：22

期号：3

起止页码：189

中文期刊名：中华传染病杂志

外文期刊名：Chinese Journal of Infectious Diseases

收录：CSTPCD、、北大核心2000、CSCD2011_2012、北大核心、CSCD

语种：中文

中文关键词：Toll样受体;D-氨基半乳糖;内毒素;急性肝损伤;表达

外文关键词：Receptors, cell surface;Endotoxins;Liver/pathology;Cytokines;Galactose

中文摘要：目的　研究D 氨基半乳糖 (D Gal) /内毒素介导的急性肝损伤模型中肝组织细胞Toll样受体 4 (TLR4 )的表达变化 ,探讨TLR4在识别内毒素、启动炎性肝损伤中的作用。方法　BALB/C小鼠腹内注射D Gal90 0mg/kg与内毒素 (即脂多糖 ,LPS) 10 μg/kg后 0～ 7h分别检测血清丙氨酸转氨酶 (ALT)及天门冬氨酸转氨酶 (AST)与血浆肿瘤坏死因子 (TNF α)含量以评价肝功能 ;另随机取10只小鼠给药后观察致死率。用半定量逆转录 聚合酶链反应 (RT PCR)和TanonGis 2 .0软件分析不同时间点肝组织中TLR4mRNA表达 ,并与血浆TNF α含量进行相关分析 ;免疫组织化学观察肝组织TLR4蛋白的表达。实验数据用SAS软件分析。结果　给药后 4h ,血清转氨酶明显升高 (与 0h比较 ,P <0 .0 5 ) ;血浆TNF α含量逐步上升 ,在 2h、5h有两个分泌高峰 ;7h小鼠开始死亡 ,10h致死率达 80 %。正常小鼠肝组织少量表达TLR4mRNA ,给药后表达明显增强 (与 0h比较 ,P <0 .0 5 ) ;免疫组织化学也显示TLR4蛋白有类似的变化 ,尤其肝窦内皮细胞、库普弗细胞表达更为显著。血浆TNF α含量与肝组织TLR4mRNA表达呈正相关。结论　肝内细胞膜上表达的TLR4可能通过启动下游的炎性应答基因表达及细胞因子释放而诱导出肝组织对LPS的炎性应答。因此 ,调控TLR4表达可能?

外文摘要：Objective In order to explore the role of Toll like receptors 4(TLR4) in recognizing endotoxin and initiating inflammatory response, the expression of TLR4 of the liver in D galactosamine(D Gal) and endotoxin induced acute hepatic injury was analyzed. Methods The BALB/C mice with acute hepatic injury were induced with the combination of D Gal(900 mg/kg)and lipopolysaccharide (LPS, 10 μg/kg) by intraperitoneal administration. To evaluate the hepatic injury, serum transaminase (ALT and AST) and plasma TNF α were determined and the mortality was observed at the various time point following intraperitoneal injection with D Gal/LPS. The level of TLR4 mRNA was measured by semiquantitative RT PCR. Also the protein expression of TLR4 in the liver was detected by immunohistochemistry. The data was analyzed by the SAS software. Results After 4 hours of intraperitoneal injection of D Gal/LPS, the serum transaminase and plasma TNF α levels were apparently elevated. The treatedmouse began to die at 7 hours. The mortality reached up to 80% at 10 hours. TLR4 mRNA were expressed at low level in normal mice liver, while it was significantly increased and maintained at higher level following intraperitoneal injection with D Gal/LPS (compare to 0 h time point, P <0.05). Similar results were obtained with the protein of TLR4 measured by immunohistochemistry. The expression of TLR4 mRNA was positively correlated with the concentration of plasma TNF α. Conclusions Our results showed that TLR4 were involved in initiating and inducing the expression of proinflammation cytokines in this model of acute hepatic injury. It suggested that TLR4 would be the novel strategy to prevent the development of infectious diseases.