外源性一氧化碳释放分子抑制脓毒症炎症反应实验探究.docVIP

外源性一氧化碳释放分子抑制脓毒症炎症反应实验探究 　 作者：孙炳伟, 陈曦, Kazuhiro Katada, Richard F Potter, Gediminas Cepinskas 【摘要】 目的： 探讨外源性一氧化碳释放分子对脓毒症炎症反应的抑制作用及可能的机制。方法： 应用盲肠结扎及穿孔脓毒症小鼠模型，使用外源性一氧化碳释放分子（CORM2, 8 mg/kg 体质量，尾静脉注射）进行干预。检测肝、肺脏髓过氧化物酶(MPO) 活性。应用内毒素(LPS，10 g/ml)刺激的人脐静脉内皮细胞炎症模型，使用外源性一氧化碳释放分子（ CORM2,10～100 mol/L）进行干预。检测核因子κB （NFκB）活性, 内皮细胞黏附分子的表达，氧化产物、NO产物以及多形核白细胞对内皮细胞的黏附作用。 结果： 盲肠结扎及穿孔脓毒症小鼠模型使用外源性一氧化碳释放分子干预后肝、肺组织MPO活性明显下降。CORM2 抑制了LPS刺激导致的 NFκB活性上调。 同时，NO产物下降，内皮细胞ICAM1的表达抑制，白细胞对内皮细胞的黏附作用明显抑制。结论： 外源性一氧化碳释放分子通过抑制NFκB 活性，抑制ICAM1 蛋白和NO的表达，抑制白细胞对内皮细胞的黏附作用，进而有效抑制脓毒症炎症反应。 【关键词】 一氧化碳； 盲肠结扎及穿孔； 炎症反应； 核因子κB CLP (cecal ligation and puncture) may induce the activation of an inflammatory cascade, cause damage to multiple organs distant from the original burn wound and may lead to sepsis and multiple organ failure［1］.There have been several reports indicating that the inflammatory response syndrome, which contributes to oxidative cell/tissue damage, might frequently be accompanied by leukocyte sequestration in many important organ systems in the body［2］.The increase of production of proinflammatory mediators such as interleukin (IL)1β and tumor necrosis factor (TNF)α is closely associated with activation of leukocytes and macrophages which were sequestrated in the tissue［3,4］. Leukocytes sequestration and their subsequent infiltration in organ tissue can cause leukocyte activation and contribute to vascular damage and the development of systemic inflammatory reaction.As the prerequisite, activation of leukocytes and endothelial cells results in aggregation of leukocytes, platelets and erythrocytes in vivo.This may favor disseminated intravasal coagulation and further multiple organ failure. Carbon monoxide (CO) has long been known in biology and medicine as a toxic compound, due to its ability to bind hemoglobin with a much higher affinity than oxygen［5］.Evidence accumulated to date suggests that endogenous carbon monoxide (CO), a biproduct of inducible heme oxygenase (H