阻断toll样受体对脂多糖致急性肺损伤的保护作用

目的：本文旨在探讨阻断toll样受体（TRL4）对脂多糖（LPS）致急性肺损伤（ALI）的保护作用。方法将60只健康雄性清洁级SD大鼠分为正常组、损伤组和阻断组，每组20只。损伤组大鼠采用尾静脉注射LPS（6mg/kg）复制ALI模型；阻断组同时注射TLR4抗体（10mg/mL）；正常组给予等容积生理盐水。3h后处死大鼠，采用凝胶滞留法检测核因子-κB（NF-κB）活性；Westernblot印记分析法检测抑制蛋白（IκB-α）水平；检测肺组织匀浆肿瘤坏死因子α细胞因子（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-10（IL-10）水平。结果与正常组相比，损伤组和阻断组肺组织湿质量/干质量比值增高，NF-κB活性升高，IκB-α、TNF-α、IL-1β水平升高（P＜0．05），而IL-10水平降低（P＜0．05）。而比较损伤组与阻断组发现，阻断组肺组织湿质量/干质量比值降低，NF-κB活性降低，IκB-α、TNF-α、IL-1β水平明显低于损伤组（P＜0．05），IL-10水平高于损伤组（P＜0．05）。结论采用抗TLR4单克隆抗体阻断TLR4介导的信号传导可明显降低NF-κB活性和IκB-α、TNF-α、IL-1β水平，同时提高IL-10水平阻断TLR4，对LPS致ALI有一定的保护作用。

Protective effect of blocking TLR4 in lipopolysaccharide induced acute lung injury

Objective To explore the protective effect of blocking TLR4 in lipopolysaccharide（LPS） induced acute lung injury（ALI） .Methods A total of 60 SD mice were randomly divided into control group ,ALI group and ALI＋ TLR4 blocking group ,with 20 mice for each group .ALI model were constructed by 6 intravenous injection of LPS（6 mg/kg） .Mice in ALI＋ TLR4 blocking group were treated with anti-TLR4 antibody（10 mg/mL） at the same time .Mice in control group were treated with normal saline for the same volume as the other 2 groups .All mice were executed 3 hours after treatment and then the activity of nuclear factor （NF）-κB ,and levels of inhibition protein κB-α（IκB-α） ,tumor necrosis factor（TNF）-α,interleukin（IL）-1βand IL-10 were detected .Results Compared with control group ,ratio of wet weight to dry weight of lung tissues ,activity of NF-κB and the expression levels of IκB-α,TNF-αand IL-1βwere significantly increased in the other two groups（P〈0 .05） ,but levels of IL-10 decreased （P〈0 .05） . Compared with ALI group ,ratio of wet weight to dry weight of lung tissues ,activity of NF-κB and the expression levels of IκB-α,TNF-αand IL-1βof ALI＋ TLR4 blocking group were decreased（P〈0 .05） ,while levels of IL-10 was increased（P〈0 .05） .Conclusion Application of monoclonal antibody to block signal pathway of TLR4 could signifi-cantly decrease the activity of NF-κB and the expression levels of IκB-α,TNF-α and IL-1β,and increase the level of IL-10 .The blockage of TLR4 might have protective effect on LPS induced ALI .