外源性一氧化碳释放分子对脓毒症小鼠肺部炎症反应的抑制作用  

Inhibition effects of carbon monoxide-releasing molecules-2 to lung inflammatory in sepsis mice

作　　者：张萍[1] 邹向前[1] 石庚生[1] 孙炳伟[1] 

机构地区：[1]江苏大学临床医学院,江苏镇江212013

出　　处：《江苏大学学报（医学版）》2010年第2期117-120,125,I0001,共6页Journal of Jiangsu University：Medicine Edition

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

摘　　要：目的:研究外源性一氧化碳释放分子(carbon monoxide-releasing molecules-2,CORM-2)干预对脓毒症小鼠肺部炎症反应的抑制作用。方法:18只雄性昆明种小鼠随机分为假手术组、CLP模型组和CORM-2干预组。制作标准盲肠结扎穿孔(cecal ligation and puncture,CLP)模型,用CORM-2进行干预,观察干预前后小鼠肺脏炎症反应的变化情况。分别于CLP术后6h,12h,24h收集血浆、取肺组织,酶联免疫吸附(ELISA)法检测血浆中肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)炎症因子的表达;检测肺组织中髓过氧化物酶(MPO)活性,观察中性粒细胞的聚集程度;测定肺组织湿干重比(W/D);苏木精-伊红(HE)染色观察肺组织病理变化;免疫组织化学法观察细胞间黏附分子(ICAM-1)、肺表面活性蛋白-A(SP-A)的表达。结果:与假手术组比较,CLP模型组主要表现为肺组织微血管通透性增加,肺泡壁增厚,间质水肿,白细胞浸润,MPO活性明显增强;炎症因子TNF-α,IL-1β和IL-6的表达水平升高(P<0.05);与CLP模型组比较,CORM-2干预组肺间质水肿程度减轻,白细胞浸润明显减少,以上炎症因子的表达明显受到抑制(P<0.05)。结论:CDRM-2可显著抑制脓毒症机体炎症细胞因子和ICAM-1、SP-A的表达,降低MPO活性,减少中性粒细胞的聚集,减轻组织炎症反应,对脓毒症小鼠肺部炎症反应有显著的抑制作用。Objective：To investigate the anti-inflammatory effects of carbon monoxide-releasing molecules-2（CORM-2） to lung inflammation in sepsis mice.Methods：Eighteen male mice were randomly divided into 3 groups：sham group,CLP group and CORM-2 group.To make standard cecal ligation and puncture models,exogenous carbon monoxide were intervened.We observed the changes in lung inflammation among those groups.After 6 h,12 h and 24 h of CLP operation,the expression of cytokines TNF-α and IL-1β in plasma samples was detected respectively by ELISA;With their pathological changes of lung tissues observed by hematoxylin-eosin staining method and their myeloperoxidase activity,neutrophils infiltration in lung tissues detected.Results：Compared with sham group,the permeability of lung tissues in CLP group increased,the alveolar wall turned thick,with interstitial edema and neutrophils infiltrated increasingly;the myeloperoxidase activity and the expression levels of inflammatory factors enhanced obviously.Contrarily,compared with CLP group,the permeability of lung tissues in CORM-2 group decreased,the alveolar wall was less thicker,interstitial edema and neutrophils infiltration were all alleviated;the myeloperoxidase activity and the expression levels of inflammatory factors decreased apparently.Conclusion：CORM-2 had significant inhibitory effects to lung inflammation in sepsis mice by alleviating the expression levels of inflammatory factors and ICAM-1,SP-A,and by decreasing the leukocyte sequestration.

关 键 词：脓毒症 肺 一氧化碳 炎症反应 

分 类 号：R631.2[医药卫生—外科学]