一氧化碳释放分子对肢体缺血一再灌注所致肺损伤的作用  

Role of CO.releasing molecule in the lung injuried by limb ischemia-reperfusion

作　　者：杨运彩[1] 周君琳[2] 黄新莉[2] 仲维佳[3] 

机构地区：[1]北京市第六医院院感办,北京100007 [2]北京朝阳医院骨科,北京100007 [3]河北医科大学病理生理教研室,北京100007

出　　处：《中华急诊医学杂志》2012年第1期43-47,共5页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金，北京市自然科学基金

摘　　要：目的观察一氧化碳释放分子（CORM）-2对大鼠肢体缺血一再灌注（I／R）所致肺损伤的作用及分子机制。方法复制大鼠双后肢缺血及再灌注后肺损伤模型。将40只SD大鼠，随机（随机数字法）分为5组（每组n=8）：假手术组（sham）、sham＋CORM-2组、I／R组、I／R＋CORM-2组、L／R＋DMSO（二甲亚砜）组。观察大鼠月市组织学、中性粒细胞（PMN）数目、肺组织湿重／干重（W／D）、丙二醛（MDA）含量、髓过氧化物酶（MPO）活性、细胞间黏附分子．1（ICAM．1）、核因子-KB（NF—KB）及其抑制因子IKBct的变化。结果IR组肺组织中PMN数目、W／D、MDA含量、MPO活性、ICAM-1表达、NF—KB活性均显著高于sham组，IKBet表达降低；再灌注前应用CORM－2可以明显逆转动物上述指标的变化，使肺损伤减轻。结论CORM-2通过抑制肢体I／R后肺内IKBa降解和NF—KB激活，下调ICAM-1表达和PMN肺内扣押，从而发挥抗肢体IR所致肺损伤的作用。Objective To observe the role and mechanism of CO-releasing molecules （CORMs） -2 in the injured lung induced by ischmia-reperfusion （IR） of hind limbs of rat. Methods The rat model of lung injury was made by ischemia in hind limbs of rat for two hours and then reperfusion for two hours as well. There were 40 SD rats randomly （ random number） divided into 5 groups （ n = 8 ）, namely sham ischemia-reperfusion （I/R） group, sham I/R ＋ CORM-2 group, I/R group, I/R ＋ CORM-2 group and I/R ＋ DMSO （Dimethylsulfoxide） group. Rats in sham I/R group underwent laparotomy without infrarenal aorta occlusion. The lung tissue structure, polymorphonuclear neutrophil （PMN） count, wet-to-dry weight ratio （W/D）, malondialdehyde （MDA） content, myeloperoxidase （MPO） activity, intercellular adhesion molecule-1 （ICAM-1）, nuclear IKBcdegradation and NF-KB activity in the lung were measured. Results Compared with the sham I/R group, the number of PMNs in lung, W/D, MDA content, MPO activity, ICAM-1 and NF-KB activity significantly increased in I/R group, whereas nuclear IKBc~ decreased （P 〈0. 01）. Compared with the I/R group, the number of PMNs in lung, W/D, MDA content, MPO activity and ICAM-1 significantly decreased in I/R ＋ COMR-2 group （ P 〈 0. 01 ）, while nuclear IKBcdncreased. Conclusions These data demonstrate that CORM-2 attenuates limb I/R-induced lung injury by inhibiting ICAM-1 protein, NF-KB pathway and the leukocytes sequestration in the lung following limb I/R in rats, suggesting that CORM-2 could be used as one of the most valuable therapeutic agents.

关 键 词：一氧化碳释放分子 肺 再灌注损伤 黏附分子 核因子-KB 

分 类 号：R363[医药卫生—病理学]