静脉注射脂多糖上调小鼠肺及肝CD14和Toll-like受体4表达  

Intravenouslylipopolysaccharide injected upregulates expressionsof CD14 and Toll-like receptor 4 inlung andliver of mice

作　　者：任大宾[1] 杜烨玮[1] 张健[2] 孙仁宇[1] 王士雯[3] 

机构地区：[1]中国医学科学院中国协和医科大学基础医学研究所病理生理学系,北京100005 [2]中国医学科学院中国协和医科大学阜外心血管病研究所,北京100037 [3]解放军总医院老年心血管病研究所,北京100853

出　　处：《基础医学与临床》2005年第4期331-336,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(30170400);国家重点基础理论研究规划项目(973)(G2000057004)

摘　　要：目的观察静脉注射脂多糖(lipopolysacchafide,LPS)致小鼠肺、肝组织及血液中LPS受体CD14、Toll-like receptor 4(TLR4)表达的变化.方法BALB/C小鼠随机分为5组,尾静脉注射LPS(7 mg/kg),分别于注后0、2、6、12和24 h取血及肺、肝组织.采用逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)及Western Blot法分别检测肺和肝组织中CD14和TLR4 mRNA及蛋白表达,血清CD14(sCD14)蛋白表达.结果CD14和TLR4 mRNA在肺、肝组织中固有表达,LPS可使肺组织CD14和TLR4表达明显上调(P＜0.05),高峰出现在2-6 h(P＜0.05),24 h降至基础水平;而肝组织的变化明显滞后于肺,12 h达高峰(P＜0.05),24 h仍高于基础水平(P＜0.05).蛋白的变化与mRNA基本一致.血清CD14的表达则随时间延长而增加.结论LPS进入体内可诱导肺、肝和血液中内毒素受体CD14和TLR4的表达.不同组织中内毒素受体表达的时间差异表明肺是内毒素血症中较早受损的器官,肺组织损伤可能进一步引发肝损伤.Objective　Tostudyexpressions of CD14 and Toll-like receptor 4 (TLR4) in blood,lung,andliverinduced-ed bylipopolysaccharide (LPS) in mice .Methods　BALB/C mice were randomly dividedintofive groups and adminis-tered withlipopolysaccharide (LPS) (7 mg/kg) fromtail vein.Samplesfromthe blood,lungandlivertissue weretakenat 0 ,2 ,6 ,12 ,or 24 h respectively after LPS administration.Semi-quantitative reverse transcription polymerase chainreaction (RT-PCR) was employedto detect the effect of LPSon mRNAlevels of CD14 and TLR4 inlungandliver .Pro-teinlevels of CD14 (sCD14) in serumand CD14 and TLR4 in the lung and liver were assessed by Western Blott .Results　CD14 and TLR4 continueusly expressedin boththe lung andliver of control mice . Whenintravenous adminis-tration of LPS was applied, mRNAexpressions of CD14 and TLR4 inthe lung were upregulated markedly (P<0·05) ,peaked at 2 ~6 h (P<0·05) ,and declinedto baseline at 24 h.However ,upregulation of mRNAexpressions of CD14and TLR4 inthe liver was remarkably delayed behindthat inthe lung,peaked at 12 h (P<0·05) and remained highoverthe base line at 24 h (P<0·05) .The protein expressions of CD14 and TLR4 in boththe lung and the liver wasconsistent withthe mRNAexpressions .SerumCD14 increased withtime going within24 h postexposureto LPS.Conclu-sion　LPSinjectedintravenously upregulates the expressions of CD14 and TLR4 inlung,liver ,and blood.The differ-ence of expressiontime for LPSreceptors in various tissues indicatedthat lung was the earlier injured organ andlungin-jury might ulteriorly elicit liver injuryin endotoxemia .

关 键 词：CD14 Toll 脂多糖 鼠肺 上调 逆转录聚合酶链式反应 E受体 receptor BALB/C小鼠 Western TLR4 mRNA 蛋白表达 基础水平 LPS受体 肝组织 尾静脉注射 chain BLOT法 内毒素受体 内毒素血症 肺组织损伤 24h 时间延长 受体表达 

分 类 号：R363[医药卫生—病理学]