脓毒症大鼠多器官Toll样受体4基因表达的改变及意义  

Changes and significance of Toll-like receptor 4 gene expression in septic rats

作　　者：鄢小建[1] 姚咏明 董宁 于燕 陆家齐 盛志勇 

机构地区：[1]解放军第三○四医院创伤外科中心免疫研究室

出　　处：《中华肝胆外科杂志》2005年第1期31-34,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：本课题受国家重点基础研究发展规划项目(编号 G1999054203);国家杰出青年基金(编号30125020);北京十五科技计划重大项目资助

摘　　要：目的　探讨脓毒症大鼠肝、肺、肾及小肠组织中Toll样受体4(TLR4)基因表达的变化 规律及其意义。方法　雄性Wistar大鼠100只,动物随机分为正常对照组、假手术组、盲肠结扎穿孔 (CLP)致脓毒症组和杀菌/通透性增加蛋白(BPI)治疗组。分别检测肝、肺、肾、小肠组织TLR4、TNF αmRNA表达以及组织、血浆中内毒素水平的改变。结果　CLP后6～12h肝、肺、肾及小肠组织 TLR4mRNA表达显著升高达峰值(P<0.05或P<0.01);BPI早期治疗可显著降低各组织内毒素 水平,CLP后12h肝、肺、肾、小肠组织和24h肾组织TLR4mRNA表达亦明显抑制(P<0.05或 P<0.01)。相关分析显示,肝、肺、肾组织TLR4mRNA表达分别与相应组织及血浆内毒素水平、组 织TNF αmRNA水平均呈显著正相关。结论　CLP后细菌内毒素可迅速侵入血循环和多种组织, 它对于诱导体内TLR4基因表达上调具有显著影响,而TLR4基因广泛表达可能参与了脓毒症的病 理生理过程。Objective To investigate the changes in tissue Toll-like receptor 4 (TLR4) gene expression and regulating mechanism in rats with sepsis induced by cecal ligation and puncture (CLP). Methods A total of 100 adult male Wistar rats were randomized into 4 groups as follows: normal control group (n=10), sham-operated group (n=10), CLP group (n=60) and bactericidal/permeability increasing protein (BPI) treatment group (n=20). Animals were sacrificed and TLR4 mRNA and TNF-α mRNA expression in tissue samples from the liver, lungs, kidneys and small intestine were measured at various intervals. Meanwhile, plasma and tissue endotoxin levels were determined at the same intervals. Results The expression of TLR4 mRNA in liver, lungs, kidneys and small intestine was significantly up-regulated and peaked at 6-12 h after CLP (P<0.05 or 0.01). Treatment with BPI could significantly reduce endotoxin levels in the liver, lungs, kidneys and inhibit expression of TLR4 in various tissue in 12 h after CLP (P<0.05 or 0.01). Furthermore, both plasma and tissue endotoxin levels and tissue TNF-α mRNA expression were markedly increased in 2 h after CLP. Significant correlation was found between tissue TLR4 mRNA expression and local TNF-α mRNA expression or endotoxin levels (P<0.01). Conclusions CLP-induced endotoxin release and distribution in various organs might play an important role in mediating excessive up-regulation of TLR4 expression, which appears to be involved in the pathogenesis of sepsis and subsequent multiple organ dysfunction syndrome.

关 键 词：脓毒症 大鼠 TOLL样受体4 基因表达 多器官功能衰竭 

分 类 号：R363[医药卫生—病理学]