N-乙酰半胱氨酸对体外循环后肺微血管通透性的保护作用

Protective effects of N-acetylcystine on pulmonary microvascular permeability of lung injury in dog after cardiopulmonary bypass

目的通过成年犬体外循环（CPB）相关肺损伤模型，研究探讨N-乙酰半胱氨酸（NAC）是否能减轻CPB相关肺损伤及保护肺微血管通透性的作用。方法成年犬24只，随机分为3组（n=8），C组（CPB中用生理盐水），N1（CPB前用NAC），N2组（CPB中用NAC）。通过监测CPB前（T0）、CPB停机后维持30min（T1）、60min（T2）的呼吸指数（RI）及肺组织中MDA的含量，检测支气管肺泡灌洗液（BALF）的白细胞计数、总蛋白含量，肺微血管通透性指数（PMPI）、电镜观察肺泡上皮细胞形态学改变。结果RI：CPB前3组差异无统计学意义，停机后（T1、T2），C组的RI升高幅度明显大于N1组、N2组（P〈0．05），N1组低于N2组（P〈0．05）。MDA：CPB前3组差异无统计学意义，停机后（T1、T2），C组MDA的升高幅度高于N1组、N2组（P〈0．05）。BALF白细胞计数、总蛋白含量：C组显著高于N1组、N2组（P〈0．05），N1组低于N2组（P〈0．05）。PMPI：C组显著高于N1组、N2组（P〈0．05），N1组低于N2组（P〈0．05）。组织学检查：C组显示明显的肺部炎症改变，还可见内皮细胞间隙增宽，Ⅱ型肺泡上皮细胞胞质空泡化，板层体消失，线粒体肿胀；N1组、N2组相应改变明显减轻。结论NAC可减轻CPB相关性肺损伤，并可降低肺微血管通透性，且CPB前NAC优于CPB中用NAC。

Objective To evaluate the protective effect on the pulmonary microvascular permeability and thereby to ameliorate the lungs injury attributed to eardiopulmonary bypass （CPB）. Method Twenty-four adult hybrid health dogs were randomly divided into three groups （8 in each group） ： group C （normal saline given after CPB）, group Nl （NAC given intravenously just before CPB） and group N2（NAC given just after CPB）. The changes of respiratory index （RI） and mallondialdehyde （MDA） content in lung tissue were observed. Samples were taken three times,before CPB （T0） ,30 min after CPB surned off （T1） and 60 min after CPB sumed off （T2）. The leucocyte count and slbumin content in bronchoalveolar lavage fluid （BALF）, the pulmonary microvascular perme- ability index （PMPI）, and the histological changes of lung under light microscope and electromicroseope in 3 groups were examined. Results No significant differences were found in the levels of RI and MDA content of lung tissue between groups before CPB. However, they gradually reduced after CPB （P 〈 0.05） in the three groups, but they still were significantly lower in group N1 and group N2 compared with those in group C at T1 and T2（ P 〈 0.05） and those in group N1 were significantly lowere than those in group N2 at T1 and T2（ P 〈 0.05）. MDA gradually increased after CPB in three groups （P 〈 0.05）, but it was still significantly lower in group N1 and group N2 than that in group C at T1 and T2 （ P 〈 0.05）. The leucocyte count and albumin content in BALF were significantly lower in group N1 and group N2 in comparison with those in group C （ P 〈 0. 05） and they were significantly lower in group N1 compared with those in group N2 （ P 〈 0. 05）. The PMPI were significantly lower in group N1 and group N2 compared with those in group C （P 〈 0.05） and they were significantly lower in group N1 compared with those in group N2（ P 〈 0.05）. By using electromicroscope,the apparent inflammatory change of lung with endothelium cellular swelling, inter-endothelial cells spaces widened, and the indistinctness, deformation or decurtation of microfilament were observed. And the dissolution of laminated body, swollen mitochondria and plasmolysis were found in alveolar epithelial ceil Ⅱ in group C. However, these changes were markedly alleviated in group N2 and group N1. Conclusions The results clearly demonstrate that NAC could protectie effect on the CPB injured lung and reduce the pulmonary microvascular permeability, and the protetive effect is better in group N1 than that in group N2.