LPS／CD14结合位点模拟肽对内毒素性大鼠急性肺损伤的治疗作用  

Therapeutic effects of mimic peptide of LBP/CD14 binding site on endotoxin-induced acute lung injure in rats

作　　者：徐智[1] 李昆霖[2] 陈锐[3] 钱桂生[1] 吴国明[1] 

机构地区：[1]第三军医大学新桥医院:全军呼吸内科研究所全军呼吸病研究重点实验室,重庆400037 [2]第三军医大学大坪医院野战外科研究所呼吸科,重庆400042 [3]第三军医大学新桥医院病理科,重庆400037

出　　处：《第三军医大学学报》2012年第24期2469-2473,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金(81070053)~~

摘　　要：目的观测LPS/CD14结合位点模拟肽(mimic peptides 12,MP12)对内毒素性急性肺损伤大鼠模型的治疗作用。方法将30只Wistar大鼠按随机数字表法分为生理盐水对照组、LPS组和LPS+MP12组(n=10)。另将40只Wistar大鼠分为两组,分别接受与LPS组和LPS+MP12组相同的处理方法,用于观测死亡率。采用LPS静脉注射法复制内毒素性急性肺损伤大鼠模型。LPS+MP12组在接受LPS注射后立即予MP12静脉注射。2 h后抽取静脉血用于检测血浆内毒素浓度。于12 h抽取动脉血,检测动脉血氧分压(PaO2)。24 h后处死各组大鼠,留取右下肺用于病理检查,右上肺匀浆检测TNF-α,留取左肺行支气管肺泡灌洗并分离肺泡巨噬细胞。采用荧光显微镜检测MP12对肺泡巨噬细胞与LPS结合的抑制作用。结果 LPS组及LPS+MP12组的血浆内毒素浓度明显高于生理盐水对照组(P<0.01),而LPS组与LPS+MP12组间血浆内毒素浓度无显著差异(P>0.05)。LPS组及LPS+MP12组PaO2显著低于生理盐水对照组(P<0.01),但LPS+MP12组PaO2显著高于LPS组(P<0.01)。LPS+MP12组肺组织TNF-α浓度及病理学评分显著低于LPS组(P<0.01)。LPS+MP12组肺泡巨噬细胞与LPS的结合率显著低于LPS组(P<0.01)。LPS+MP12组的72 h死亡率显著低于LPS组(40%vs 75%,P<0.01)。结论 LPS/CD14结合位点模拟肽(MP12)能通过阻断内毒素与肺泡巨噬细胞的结合,减轻内毒素导致的肺部炎症及病理损害,显著提高内毒素性急性肺损伤大鼠的动脉血氧分压、减少死亡率。Objective To determine the therapeutic effect of a mimic peptide （mimic peptides 12, MP12） of LBP/CD14 binding site on LPS-indueed acute lung injure （ALl） in rat model. Methods Thirty Wistar rats were divided randomly into control group, LPS group and LPS ＋ MP12 group. Another forty Wistar rats were divided randomly into 2 groups and accepted the same treatment as LPS group and LPS ＋ MP12 group respectively in order to observe the mortality. The rat ALI model was established by intravenous injection of LPS. The rats of LPS ＋ MP12 group accepted MP12 intravenous injection immediately after LPS injection. In 2 h later, blood sample of each group rats were collected to detect the concentration of endotoxin. Arterial blood samples were collected to detect PaO2 in 12 h after LPS injection. All rats were executed in 24 h, the right lower lung was embedded for pathological examination, and the right upper lung was used to measure TNFot content. The left lung was used for bronchoalveolar lavage and isolation of alveolar macrophages. The effect of MP12 on the binding between LPS and alveolar macrophages was observed by fluorescence microscopy. Results The endotoxin level in the plasma was significantly higher in LPS group and LPS ＋ MPI2 group than control group （P 〈 0. 01 ）, but there was no significant difference in the former 2 groups （ P 〉 0. 05 ）. PaO2 value was significantly lower in LPS group and LPS ＋ MP12 group than in control group （P 〈 0. 01 ）, and, the value was significantly higher in of LPS ＋ MP12 group than LPS group （P 〈 0. 01 ）. TNFα content in lung tissue and the pathological score were significantly lower in LPS ＋ MP12 group than LPS group （ P 〈 0. 01 ）. The binding between LPS and alveolar macrophages was significantly lower in LPS ＋ MP12 group than LPS group （P 〈 0. 01 ）. The mortality of LPS ＋ MP12 group were significantly lower than that of LPS group （40% vs 75% , P 〈0. 01 ）. Conclusion The mimic peptide of LPS/CD14 binding site bl

关 键 词：内毒素 CD14 模拟肽 急性肺损伤 

分 类 号：R563.05[医药卫生—呼吸系统] R631[医药卫生—内科学]