阻断toll样受体对脂多糖致急性肺损伤的保护作用  

Protective effect of blocking TLR4 in lipopolysaccharide induced acute lung injury

作　　者：姚亚奔[1] 黄继义[2] 刘才文[2] 林建东[3] 叶先龙[2] 洪朝基 周荣[5] 

机构地区：[1]厦门大学附属第一医院同民分院急诊科,福建厦门361000 [2]厦门大学附属第一医院同民分院内科,福建厦门361000 [3]福建医科大学附属第一医院ICU,福州350000 [4]厦门医科所内科,福建厦门361000 [5]厦门大学附属第一医院急诊科,福建厦门361000

出　　处：《检验医学与临床》2014年第9期1171-1172,共2页Laboratory Medicine and Clinic

基　　金：福建省厦门市翔安区科技局资助项目(350213X)

摘　　要：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;Western blot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。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 .

关 键 词：急性肺损伤 TOLL样受体 单克隆抗体 信号传导 

分 类 号：R392.11[医药卫生—免疫学]