外源性一氧化碳释放分子2对脓毒症大鼠肺炎症反应的抑制作用及分子机制

Carbon monoxide-releasing molecule-2 inhibits the inflammatory response in the lung of sepsis rat

目的:观察外源性一氧化碳释放分子2(carbon monoxide-releasing molecules-2,CORM-2)干预对脓毒症大鼠肺部炎症反应的抑制作用并探讨其机制。方法:24只雄性SD大鼠随机分为假手术组、CLP组和CLP+CORM-2组。采用盲肠结扎穿孔(cecal ligation and puncture,CLP)法建立脓毒症模型,用CORM-2进行干预,苏木精-伊红(HE)染色观察肺组织病理变化;放射免疫法检测血浆中TNF-α和白细胞介素(IL-1β、IL-6)的变化;ELISA法检测肺组织细胞间黏附分子-1(ICAM-1)的含量,蛋白质印迹法检测肺组织核因子-κB(NF-κB)蛋白的表达情况。结果:与假手术组相比,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,炎症因子TNF-α、IL-1β、IL-6的水平明显增加,ICAM-1含量明显增高,NF-κB表达水平明显增加(P均<0.01);CLP+CORM-2组肺间质轻度水肿,白细胞少量浸润,炎症因子的表达增加,ICAM-1含量增高,NF-κB表达水平增加(P均<0.05)。与CLP模型组比较,CLP+CORM-2组肺间质水肿程度减轻,白细胞浸润明显减少,炎症因子水平显著下降,ICAM-1含量下降,NF-κB表达水平明显下降(P均<0.05)。结论:CDRM-2可显著抑制脓毒症大鼠肺部炎症反应,其可能机制为CORM-2可有效地减弱NF-κB的表达。

Objective： To investigate the anti-inflammatory effects of carbon monoxide-releasing molecules-2（CORM-2） on lung inflammation in sepsis rat.Methods： Twenty-four Sprague Dawley rats were randomly divided into 3 groups： ①sham group,②cecal ligation and puncture（CLP） group and ③CLP＋CORM-2 group.To make standard cecal ligation and puncture models,exogenous carbon monoxide was intervened.After 48 h of CLP operation,their pathological changes of lung tissues observed and the expression of TNF-α、IL-1β and IL-6 in plasma samples was detected respectively by radioimmunoassay;Level of intercellular adhesion molecule-1（ICAM-1） in the lung was assessed by ELISA;Expression of NF-κB was assessed by Western-blot.Results： In CLP group the permeability of lung tissues increased,the alveolar wall turned thick,with interstitial edema and Europhiles infiltrated increasingly;the expression levels of inflammatory factors and ICAM-1 enhanced obviously,this was accompanied by an increase of the expression of NF-κB.Compared with CLP group,the permeability of lung tissues in CORM-2 group markedly decreased,the alveolar wall was less thicker,interstitial edema and Europhiles infiltration were all alleviated;the expression levels of inflammatory factors decreased apparently,the level of ICAM-1 in the lung and expression of NF-κB were decreased obviously.Conclusion： CORM-released CO attenuates the inflammatory response in the lung of CLP rats by anti-NF-κB.