CAJ | 학술논문

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（6 mg/kg）复制ALI模型；阻断组同时注射TLR4抗体（10 mg/mL）；正常组给予等容积生理盐水。3 h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（T N F-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，N F-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T L R4介导的信号传导可明显降低N F-κB活性和IκB-α、T N F-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。
목적：본문지재탐토조단 toll양수체（TRL4）대지다당（LPS）치급성폐손상（ALI）적보호작용。방법장60지건강웅성청길급SD대서분위정상조、손상조화조단조，매조20지。손상조대서채용미정맥주사LPS（6 mg/kg）복제ALI모형；조단조동시주사TLR4항체（10 mg/mL）；정상조급여등용적생리염수。3 h후처사대서，채용응효체류법검측핵인자-κB（NF-κB）활성；Western blot인기분석법검측억제단백（IκB-α）수평；검측폐조직균장종류배사인자α세포인자（T N F-α）、백세포개소-1β（IL-1β）화백세포개소-10（IL-10）수평。결과여정상조상비，손상조화조단조폐조직습질량/간질량비치증고，NF-κB활성승고，IκB-α、TNF-α、IL-1β수평승고（P＜0．05），이IL-10수평강저（ P＜0．05）。이비교손상조여조단조발현，조단조폐조직습질량/간질량비치강저，N F-κB활성강저，IκB-α、TNF-α、IL-1β수평명현저우손상조（P＜0．05），IL-10수평고우손상조（P＜0．05）。결론채용항 TLR4단극륭항체조단T L R4개도적신호전도가명현강저N F-κB활성화IκB-α、T N F-α、IL-1β수평，동시제고IL-10수평조단TLR4，대LPS치ALI유일정적보호작용。
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 .