小鼠全肝缺血再灌注时肺泡巨噬细胞TLR2的激活与肺损伤的机制  

The mechanism of TLR2 activation and lung injury during the process of total hepatic ischemia/reperfusion in mice

作　　者：谷元廷[1] 吴河水[1] 徐建波[1] 王琳[2] 田元[1] 王春友[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院普通外科 [2]华中科技大学同济医学院附属协和医院儿科,湖北武汉430022

出　　处：《中国普通外科杂志》2006年第12期920-922,共3页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(30200272)

摘　　要：目的探讨肺泡巨噬细胞Toll样受体2(TLR 2)的激活机制及其在肝脏缺血再灌注(HIR)中肺损伤的意义。方法用野生型小鼠C 3 h/Heouj和TLR 4缺失小鼠C 3 h/Hej建立HIR动物模型。于再灌注1,6,1 2 h后经支气管肺泡灌洗液获取肺泡巨噬细胞,采用荧光定量PCR方法检测TLR 2/4mRNA的表达。同时检测支气管肺泡灌洗液中内毒素及肿瘤坏死因子(TNF)的水平,肺组织湿干重比值,肺组织髓过氧化物酶的浓度,并进行肺组织学评分。结果C 3 h/Heouj组HIR缺血再灌后各时点肺泡巨噬细胞TLR 2/4mRNA表达升高,TLR 2mRNA表达持续升高,TLR 4mRNA 6 h达到最高值。同时C 3 h/Heouj组HIR后支气管肺泡灌洗液中TNF水平明显升高,肺损伤加重,肺组织湿干重比值持续升高,肺组织髓过氧化物酶持续增加(P<0.0 5)。C 3 h/Hej组HIR后TLR 2mRNA表达仅轻度升高,且支气管肺泡灌洗液中TNF水平低于C 3 h/Heouj组(P<0.0 5),肺损伤轻于C 3 h/Heouj组(P<0.05)。结论HIR可致肺泡巨噬细胞表面TLR 4的激活,可上调TLR 2的表达,从而可加重HIR时的肺损伤。Objectlve To explore the mechanism of the activation of Toll-like receptor 2 in alveolar macrophage and its significances in hepatic ischemia/reperfusion （HIR） associated lung injury in mice. Methods Wild type mice （C3 h/Heouj ）and TLR4-deficient mice （C3 h/HeJ ） were used in a model of hepatic ischemia/reperfusion. Alveolar macrophages were collected at the time point of 1 h, 6h and 12h after HIR by means of bronchoalveolar lavage （ BAL ） , and the expression of TLR2/4 mRNA was detected with Real-Time PCR. The level of endotoxin and TNF-ct in BAL fluid were measured. The concentration of MPO, the ratio of wet/dry weight of lung tissue, and lung histological scores were used to assess the degrees of lung injuries. Results The expressions of TLR2/4 mRNA in HIR group of C3h/Heouj mice were up-regulated at the all three time points after HIR. The level of TLR2 mRNA was increased sustainedly and TLR4 markedly increased at 6 h （ P 〈 0. 01 ）. At the same time TNF-α concentrations in BALF were increased （ P 〈 0. 01 ） and lung injuries were aggravated which was indicated by the level of MPO, the ratio of wet/ dry weight of lung and lung histological scores. But in TLR4-deficient （C3 h/Hej ） animals, the activations of TLR2 after HIR were only slight increased. TNF-α levels were significantly decreased compared to wild type mice at three time points after reperfusion （ P 〈 0.01 ） , and lung injuries were milder than that in wild typy mice （ P 〈 0.05 ）. Conclusions Toll-like receptor 2 on alveolar macrophage can up-regulate TLR4 expression after HIR, which can aggravated the injury of the lung.

关 键 词：受体 Toll 肝 再灌注损伤 肺损伤 巨噬细胞 肺泡 

分 类 号：R657.3[医药卫生—外科学] R602[医药卫生—临床医学]