内源性一氧化氮抗兔肺缺血再灌注损伤作用及其机制探讨

目的　探讨内源性一氧化氮在兔肺缺血再灌注过程中有无抗肺损伤作用及可能的机制。方法　制备兔缺血再灌注损伤模型 ,32只新西兰大白兔随机分为对照组即假手术组 (Sh O)、肺缺血再灌注组 (L IR)、L IR 左旋精氨酸 (L- Arg)组 (静脉注入 NO合成的底物 L- Arg2 0 0 mg/ kg)、L IR 左旋硝基精氨酸 (L- NNA)组 (静脉注入NO合成抑制剂 L- NNA10 0 mg/ kg)。大白兔在肺动脉再灌注 6 0 m in后立即取肺组织观察各组病理改变、肺湿重 /干重比值 (W/ D) ,检测各组肺组织内髓过氧化物酶 (MPO)活性、丙二醛 (MDA)含量及硝酸盐 /亚硝酸盐 (N/ N)比值。结果　与 Sh O组比较 ,L IR组肺水肿明显 ,W/ D比值上升、MPO活性及 MDA含量增高 ,而 N/ N下降 (P<0 .0 1) ;与 L IR组比较 ,L IR L - Arg组肺水肿减轻 ,MPO活性及 MDA含量下降 ,N/ N量增加 (P<0 .0 1) ;与 L IR或 L IR L - Arg组比较 ,L IR L - NNA组肺水肿更加严重 ,MPO活性及 MDA含量增高更明显 (P<0 .0 1)。结论内源性 NO的释放可减轻肺缺血 -再灌注损伤 ,其作用机制与抑制中性粒细胞在肺内的聚集 ,降低血管通透性 ,对抗氧自由基造成的肺损伤有关。

The Protective Efficacy of Rabbit Endogenous Nitric Oxide Against Acute Rabbit Lung Ischemia-Reperfusion Injury and Its Mechanism

Objective To investigate the protective efficacy of rabbit endogenous nitric oxide (NO) against acute rabbit lung injury associated with ischemia-reperfusion and explore the possible mechanism. Methods The rabbit lung ischemia-reperfusion(LIR) model was established; thirty-two adult Newzeland white rabbits were randomly divided into four groups. The rabbits of control group underwent sham operation. In group LIR, the rabbits' left lung hili were clamped for 60 minutes and then released. In group LIR L-Arg(L-arginine), the rabbits were operated upon as those in group LIR, but L-Arg (200 mg/kg) was infused into blood circulation as substrate for NO generation before removal of the clip. In group LIR L-NNA (L-ng-nitro-Arginine), the rabbits passed through the same operation as in group LIR, but L-NNA (10 mg/kg) was infused into circulation as an inhibitor against NO generation before reperfusion. After reperfusion for 60 minutes, the lung tissues were harvested for histological examination, and the wet to dry ratio of lung tissue weight (W/D), myeloperoxidase(MPO) activity, malondialdehyde(MDA)content as well as the ratio of nitrate/nitrite(N/N) were measured respectively. Results The group LIR had greater lung tissue W/D, higher MPO activity and MDA content, lower ratio of N/N, and serious pulmonary edema as compared with group ShO(P<0.01). But in group LIR L-Arg, the degree of pulmonary edema was alleviated, the MPO activity and MDA content were decreased, and the ratio of N/N increased; there was statistically significant difference between group LIR and group LIR Arg in respect to the above indices(P<0.01). However, in group LIR L-NNA, the pulmonary edema was even more severe, the MPO activity and MDA content were significantly higher those that in group LIR or group LIR L-Arg(P<0.01). Conclusion The endogenous release of pulmonary NO can attenuate the acute lung injury associated with LIR, and the mechanisms may involve the protective efficacy conferred by endogenous NO against accumulation of neutrophil in lung, against pulmonary microvascular permeability, and against the oxygen free radical injury to lung.