脂多糖结合蛋白抑制肽对脂多糖与内毒素血症小鼠肺泡巨噬细胞结合的影响  

Effects of lipopolysaccharide-binding protein inhibitory peptide on the binding of lipopolysaccharide to alveolar macrophages in a mouse model of endotoxemia

作　　者：吴学玲[1] 赵云峰[2] 钱桂生[1] 徐德彬[1] 陈维中[1] 

机构地区：[1]第三军医大学附属新桥医院呼吸病研究所,重庆400037 [2]东南大学中大医院呼吸科

出　　处：《中国呼吸与危重监护杂志》2008年第3期195-198,217,I0001,共6页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：国家自然科学基金资助项目(编号:30170366)

摘　　要：目的研究脂多糖结合蛋白(LBP)抑制肽P12对脂多糖(LPS)与小鼠肺泡巨噬细胞(AMs)结合的抑制作用,探讨LBP抑制肽体内阻断内毒素信号传导通路的机制。方法40只小鼠随机分为5组:对照组、内毒素血症组、低剂量P12组、中剂量P12组和高剂量P12组,每组8只。腹腔内注射LPS复制内毒素血症模型,尾静脉注射P12,流式细胞检测分析(FACS)异硫氰酸荧光素标记的LPS(FITC-LPS)与AMs的结合,以平均荧光强度(MFI)表示;ELISA法检测小鼠血清中肿瘤坏死因子α(TNF-α)的含量。结果内毒素血症组小鼠AMsMFI明显高于对照组(45.31%比4.61%,P<0.05);低剂量P12组、中剂量P12组和高剂量P12组的MFI分别为40.08%、30.76%和24.45%,低于内毒素血症组(低剂量组P>0.05,中剂量P12组和高剂量组P均<0.05)。内毒素血症组小鼠血清中TNF-α的含量显著高于对照组[(180.17±39.14)pg/mL比(24.88±5.82)pg/mL,P<0.01];低剂量P12组、中剂量P12组和高剂量P12组血清中TNF-α的含量分别为(112.69±19.78)pg/mL、(86.34±9.25)pg/mL和(70.48±8.48)pg/mL,均明显低于内毒素血症组(P均<0.05)。结论LBP抑制肽P12抑制了LPS与内毒素血症小鼠AMs的结合,显著降低了LPS诱导的TNF-α的产生。Objective To investigate whether P12,a kind of lipopolysaccharide（LPS）-binding protein（LBP） inhibitory peptide,could suppress the binding of LPS to alveolar macrophages（AMs） in a mouse model of endotoxemia in vivo.Methods Forty mice were randomly divided into five groups,ie.a control group,an endotoxemia group,a low dose P12-treated group,a middle dose P12-treated group and a high dose P12-treated group.Mouse model of endotoxemia was established by LPS injection intraperitoneally in the endotoxemia group and P12-treated groups.P12 was instilled via the tail vein.The effects of P12 on the binding of LPS to AMs were determined by flow cytometric analysis and quantization by mean fluorescence intensity（MFI）.The productions of tumor necrosis factor α（TNF-α） in serum of mice were measured by enzyme-linked immunosorbent assay（ELISA）.Results MFI in AMs from low,middle and high dose P12-treated groups was 40.08%,30.76% and 24.45%,respectively,which was higher than that of the control group（4.61%）,but less than that of the endotoxemic mice（45.31%）.The concentration of TNF-α in serum of low,middle and high dose P12-treated mice was（112.69±19.78）pg/mL,（86.34±9.25） pg/mL,（70.48±8.48）pg/mL respectively,which was higher than that of the control group[（24.88±5.82）pg/mL],but less than that of the endotoxemic mice[（180.17±39.14）pg/mL].Conclusion The results suggest that P12 inhibit the binding of LPS to AMs,thus reduce the proudction of TNF-α stimulated by LPS.

关 键 词：内毒素血症 脂多糖结合蛋白抑制肽 脂多糖 肿瘤坏死因子Α 

分 类 号：R563[医药卫生—呼吸系统]