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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。
Objective: To investigate the inhibitory effect of exogenous carbon monoxide releasing molecule on sepsis inflammatory reaction and its possible mechanism. Methods: The cecal ligation and perforation sepsis mice model were induced by exogenous carbon monoxide release (CORM-2, 8 mg / kg body weight, tail vein injection). Liver and lung myeloperoxidase (MPO) activity was detected. The model of human umbilical vein endothelial cells stimulated by endotoxin (LPS, 10 g / ml) was used and the intervention of exogenous carbon monoxide releasing molecule (CORM-2, 10-100 mol / L) was used. The activity of nuclear factor kappa B (NF-κB), the expression of endothelial cell adhesion molecules, the products of oxidation, the production of NO and the adhesion of polymorphonuclear leukocytes to endothelial cells were detected. Results: The MPO activity in the liver and lung tissues of the cecal ligation and perforated sepsis mice model was significantly reduced by exogenous carbon monoxide releasing molecule. CORM-2 inhibited the up-regulation of NF-κB activity induced by LPS stimulation. At the same time, the NO production decreased, the expression of ICAM-1 in endothelial cells was inhibited, and the adhesion of leukocytes to endothelial cells was significantly inhibited. CONCLUSION: Exogenous carbon monoxide releasing molecule inhibits the adhesion of leukocytes to endothelial cells by inhibiting the activity of NF-κB, inhibiting the expression of ICAM-1 protein and NO, and then inhibiting the inflammatory response of sepsis effectively.