外源性一氧化碳抗大鼠肢体缺血再灌注所致肺损伤的实验研究

Exogenous carbon monoxide protects against the lung injury induced by ischemia-reperfusion of hind limbs in rats

目的:观察外源性一氧化碳(CO)对大鼠肢体缺血再灌注(IR)所致肺损伤的作用及机制。方法:32只SD大鼠,随机分为4组(每组n=8):对照组(control)、control+CO、IR和IR+CO组。复制大鼠双后肢缺血及再灌注后肺损伤模型。IR+CO和control+CO组在再灌注前1h或相应时点置含2·5×10-8CO的空气中,其余两组呼吸正常空气。观察大鼠肺组织学、肺组织中中性粒细胞(PMN)数目、丙二醛(MDA)含量、肺组织湿重和干重之比(W/D)以及动物生存情况等。应用一氧化碳血氧分析仪监测动脉血中碳氧血红蛋白(COHb)水平的变化;应用Western blot-ting检测肺组织中细胞间粘附分子-1(ICAM-1)表达的变化。结果:IR组动物死亡率、肺组织中PMN数目、W/D、MDA含量和ICAM-1表达均显著高于control组;IR+CO组血内COHb水平显著高于IR组,而上述指标则均显著低于IR组、肺损伤减轻。结论:外源性CO可减轻肢体IR所致肺损伤,其机制可能与下调ICAM-1表达、抑制PMN在肺内聚集有关。

AIM： To study the mechanism of protective effect of exogenous carbon monoxide （CO） in the lung injury induced by isehemia - reperfusion （IR） of hind limbs in rats. METHODS： Thirty - two SD rats were randomly divided into 4 groups： control, eontrol＋ CO, IR and IR ＋ CO. A rat model of isehemia in hind limbs and the reperfusion lung injury was made. The rats in IR ＋ CO and control ＋ CO groups were exposed to air containing 2.5 × 10^-8 CO for 1 h before reperfusion or the corresponding control time point, while the other two groups were exposed to the routine air. The lung tissue structure, polymorphonuclear leukocyte （PMN） count, wet- to- dry weight ratio （W/D）, malondialdehyde （MDA） content and the animal survival rate were observed. The caiboxyhemoglobin （COHb） levels in artery blood were detected with CO - oximeter and the expression of intercellular adhesion molecule- 1 （ICAM- 1） in the lung was detected by Western blotting. RESULTS： Compared to control, the animal mortality, lung PMNs number, W/D, MDA content and ICAM - 1 expression were all significantly increased in IR group. Compared with the IR group, the blood COHb level was significantly increased and the animal mortality, lung PMNs number, W/D, MDA content and ICAM - 1 expression were all significantly decreased in IR ＋ CO group. CONCLUSION： These data suggest that exogenous CO attenuate limb IR- induced lung injury by down- regulatiny ICAM- 1 expression and suppressing PMN sequestration in the lung following hmb IR in rats.