急性腹腔感染早期大鼠肠黏膜屏障中Toll样受体信号通路的变化及意义  

Effect of TLR signaling pathway in intestinal mucosal barrier of rat during early phase of sepsis by CLP

作　　者：李国逊[1] 钮凌颖[1] 杨荣[1] 龚剑锋[1] 李宁[1] 

机构地区：[1]南京军区南京总医院解放军普通外科研究所,江苏南京210002

出　　处：《肠外与肠内营养》2011年第1期31-34,38,共5页Parenteral & Enteral Nutrition

基　　金：国家自然科学基金资助(30972880;30901420)

摘　　要：目的:初步探讨在急性腹腔感染时肠上皮细胞Toll样受体(TLR)及其下游信号分子的表达规律及对肠黏膜屏障的作用。方法:将大鼠随机分为对照组和实验组,实验组又按手术后时间分为2 h组、6 h组、12 h组和24 h组。实验组采用盲肠结扎穿孔模型,并检测各组末端回肠黏膜上TLR2、TLR4和TLR9的mRNA表达情况,NF-κB的活性,血清IL-6和TNF-α水平以及肠道的通透性水平。结果:随着腹腔感染时间的延长,TLR2的mRNA表达逐渐增高,至12 h最高,随后略有下降,与对照组相比,自6 h开始其间有极显著性差异(P≤0.01);TLR4的mRNA表达6 h达高峰,与对照组比有极显著性差异(P≤0.01);TLR9的mRNA表达12 h达高峰,与对照组比有显著性差异(P≤0.05)。TLR2与肠道通透性的相关性明显高于TLR4和TLR9。结论:重度腹腔感染早期,肠道中的TLR就可能通过调节促炎因子和炎性因子来调控肠黏膜屏障的通透性,其中TLR2起着更关键的作用。Objective： Failure of the gut barrier and intra-abdominal infection have been implicated in sepsis and multiple organ failure（MOF） syndromes in adults.TLRs signaling pathway has taken a key role in many infection reactions,but the contributions of TLRs signaling pathway to the pathophysiology of disease and the outcomes of it in the sepsis are not clear.The aim of this study is to discover the regularity of TLRs in gut mucosa and the role of TLRs signaling pathway in mucosal barrier during early phase of sepsis.Methods： Sprague Dawley rats were randomly allocated into control group（n=6）,or experimental group（n=24）.In CLP model,the rats in experimental group were randomly allocated into group 2 h（n=6）,group 6 h（n=6）,group 12 h（n=6）,or group 24 h（n=6）,according to the time.The inflammatory cytokines,accompanied by gut mucosal permeability using an in situ loop preparation of gut with fluorescence isothiocyanate-conjugated dextran,were measured.We further determined the level of TLR2,TLR4,and TLR9 in gut mucosa using a fluorescent RT-PCR.Results： The level of TLR2 in experimental group was significantly higher than that in control group on 6 hour,12 hour,and 24 hour（P≤0.01）,and the peak was found on 12 hour.Similarly,the peak of TLR4 was found on 6 hour,and the level of TLR4 in experimental group was significantly higher than that in control group on 6 hour（P≤0.01）.The changing trend of TLR9 did not have apparent regularity,but the expression of TLR9 in experimental group still had a peak on 12 hour,and was higher than that in control group（P≤0.05）. Conclusions： These findings indicate that the TLRs in gut mucosa can adjust the mucosal permeability through modifying inflammatory cytokines in the early phase of intra-abdominal infection,and TLR2 signaling pathway maybe take more important role in this process.

关 键 词：TOLL样受体 感染 肠黏膜功能 信号通路 

分 类 号：R63[医药卫生—外科学]