外源性一氧化碳释放分子2对急性肺损伤时肺部炎症反应的抑制作用  

Inhibitory effect of extrinsic CO-releasing molecules-2(CORM-2) on inflammatory responses in mice with LPS-induced acute lung injury

作　　者：孙炳伟[1] 王波[1] 杨国涛[1] 王敏[1] 仇雪峰[1] 孙艳[1] 陈曦[1] 

机构地区：[1]江苏大学附属医院烧伤整形科,江苏镇江212001

出　　处：《浙江大学学报（医学版）》2010年第5期458-463,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(30772256);江苏省自然科学基金(BK2008237)

摘　　要：目的:探讨外源性一氧化碳释放分子(CORM)2对急性肺损伤(ALI)时肺部炎症反应的抑制作用。方法:建立小鼠LPS吸入肺损伤模型。实验动物分成4组:对照组(n=8),LPS吸入致ALI组(n=15),ALI+无活性CORM-2组(n=15)以及ALI+CORM-2组(n=15)。在自制的16cm×8 cm雾化发生罐中雾化LPS(终浓度500μg/ml),实验组小鼠在雾化罐中放置30 min,对照组小鼠置于单纯的生理盐水雾化罐30 min,ALI+CORM-2组小鼠尾静脉注射CORM-2(8 mg/kg)。检测动物肺组织髓过氧化物酶(MPO)、核因子κB(NF-κB)活性、细胞间粘附分子-1(ICAM-1)的表达,肺泡灌洗液中TNF-α和IL-1β水平。结果:ALI组肺组织中MPO及NF-κB活性迅速增强,同时肺组织ICAM-1蛋白水平亦显著升高。CORM-2干预后肺组织MPO及NF-κB活性被明显抑制(P<0.05),ICAM-1蛋白表达量也被显著抑制(P<0.05)。肺泡灌洗液中TNF-α和IL-1β水平在CORM-2干预后较ALI组明显下降(P<0.05)。结论:外源性一氧化碳释放分子能明显抑制肺组织NF-κB活性,减轻ALI肺组织粘附分子的表达,从而减轻组织中白细胞扣留,有效减轻肺部炎症反应。Objective： To investigate the effects of extrinsic CO-releasing molecules-2（CORM-2） on attenuating pulmonary injury and the inflammatory response in LPS-induced acute lung injury of mice.Methods： Fifty-three mice were assigned to four groups.Mice in sham group（n=8） underwent sham inhalation,whereas mice in ALI（n=15） received inhalation of LPS for 30 min,mice in ALI＋iCORM（n=15） underwent LPS inhalation with immediate administration of inactive CORM-2（8mg/kg,i.v.）,mice in ALI＋CORM（n=15） underwent LPS inhalation with immediate administration of CORM-2（8mg/kg,i.v.）.PMN accumulation（MPO assay） in mice lungs and TNF-α and IL-1β in BAL fluid were determined.Activation of NF-κB and expression level of ICAM-1 in the lung were assessed.Results： Treatment of ALI mice with CORM-2 attenuated PMN accumulation and prevented activation of NF-κB in the lung.This was accompanied by a decrease of the expression of ICAM-1.In parallel,CORM-2 markedly decreased the production of inflammatory mediators in BAL fluid.Conclusion： CORM-2 attenuates the inflammatory response in the lung of LPS-induced ALI by decreasing leukocyte sequestration and interfering with NF-κB activation,expression of ICAM-1 and therefore suppressing endothelial cells pro-adhesive phenotype.

关 键 词：一氧化碳/治疗应用 肺/损伤 肺/药物作用 NF-ΚB 胞间粘附分子1 

分 类 号：R563.8[医药卫生—呼吸系统]