LBP抑制肽对内毒素诱导的脓毒血症小鼠的保护作用  

LBP inhibitory peptide protect mice induced by lipopolysaccharide from sepsis

作　　者：吴学玲[1] 赵云峰[2] 钱桂生[1] 徐德彬[1] 

机构地区：[1]第三军医大学新桥医院全军呼吸病研究所,重庆400037 [2]东南大学附属中大医院呼吸内科,江苏南京210009

出　　处：《中国现代医学杂志》2009年第11期1636-1639,共4页China Journal of Modern Medicine

基　　金：国家自然科学基金资助课题(No:30170366)

摘　　要：目的研究脂多糖结合蛋白抑制肽(P12)对内毒素脂多糖(LPS)诱导的脓毒血症小鼠TLR4、CD14及肿瘤坏死因子α(TNFα)表达和小鼠生存率的影响。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复制脓毒血症模型,尾静脉注射P12,蛋白定量方法(Western blot)检测TLR4和CD14蛋白的表达,ELISA法检测小鼠血清中TNF-α的含量。结果抑制肽组TLR4和CD14蛋白的OD值较LPS组低,较正常组高。脓毒血症组小鼠血清中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)、(86.34±9.25)和(70.48±8.48)pg/mL,均明显低于脓毒血症组(均P<0.05)。结论脂多糖结合蛋白抑制肽通过抑制由TLR4和CD14介导的LPS跨膜信号转导,降LSP诱导的TNFα的释放,提高了脓毒血症小鼠的生存率。表明脂多糖结合蛋白抑制肽对急性肺损伤或脓毒血症可能具有潜在的预防和早期治疗作用。[Objective] To investigate the effects of LBP inhibitory peptide on lipopolysaccharide-induced signal- ing in mice. [Methods] A total of 70 Kunming mice （8-12 weeks old） were used in our experiments. The production of CD4 and TLR4 in mice lung was detected by Western blotting. The production of tumor necrosis factor-alpha （TNF） was measured by ELISA. Differences among groups were determined using one-way ANOVA test and Fisher exact test. [Results] P12 inhibited the production of CD14 and TLR4 in mice lung and the productions of TNF-indueed by LPS were also significantly suppressed by P12. Furthermore P12 protect mice from LPS-induced death. [Conclusion] The results suggest that blockade of LBP at the inflammation sites might attenuate LPS-induced circulatory shock. This results in a beneficial effect in a mouse model of sepsis.

关 键 词：脂多糖结合蛋白抑制肽 脂多糖 TLR4 CD14 肿瘤坏死因子Α 

分 类 号：R-332[医药卫生] R392.11