吸入一氧化氮对感染性急性肺损伤时红细胞变形能力的影响

Effects of inhaled nitric oxide on erythrocyte deformability in septic acute lung injury

目的研究吸入一氧化氮（NO）对红细胞变形能力的影响及其可能机制。方法将3～4周龄健康雄性幼猪30只麻醉后经口气管插管进行机械通气，随机分为4组。（1）正常组（C，n=6）单纯机械通气；（2）正常幼猪加吸入NO（CNO，n=4）；（3）模型组（M，n=10）单纯机械通气；（4）模型制备加吸入NO（MNO．n=10）。M和MNO组动物经腹腔注射标准大肠杆菌诱发急性肺损伤（ALI），C及CNO组用无菌生理盐水替代。MNO组出现ALI后进行吸入NO（10×10^-6），治疗24h，CNO组则机械通气4h后（0h）开始吸入NO并维持24h。在实验基础状态、ALI时（0h）、ALI后12以及24h测血细胞比容、全血黏度、红细胞膜Na^＋-K^＋-ATP酶、Ca^2＋-Mg^2＋-ATP酶活性及红细胞内丙二醛（MDA）浓度。结果CNO组吸入NO后12、24h高切率下血液黏度（反映红细胞变形能力）、红细胞膜Na^＋-K^＋-ATP酶、Ca^2＋-Mg^2＋-ATP酶活性及红细胞内MDA浓度变化不大。动物出现ALI时其红细胞变形能力降低，红细胞膜Ca^2＋-Mg^2＋-ATP酶、Na^＋-K^＋-ATP酶活性均下降，红细胞内MDA浓度升高（P〈0．05）。MNO组在吸入NO12h时红细胞变形能力改善，红细胞膜Ca^2＋-Mg^2＋-ATP酶、Na^＋-K^＋-ATP酶活性均较M组高（P〈0．05），红细胞内MDA浓度则低于M组（P〈0．05）；但这些参数在吸入NO24h与C组比较差异均无显著性（P〉0．05）。结论ALI时红细胞变形能力显著下降，可以因吸入NO而改善，但作用不持久。

Objective To investigate the effects and related mechanism of iNO on erythrocyte deformability in septic acute lung injury（ALI）. Methods Thirty anesthetized and mechanically ventilated young piglets（3-4weeks old） were allocated to 4 groups： （1） normal（ group C, n=6） ：intraperitoneal injection of normal saline（NS）. （2） normal＋iNO（group CNO, n=4）：NS followed by mechanical ventilation for 4 h, and then treated with i NO at 10 parts per million in volume（ppm）. （3） model（ group M, n=10） ：i. p. Escherichia coli at 5×10^9 cfu/ml, 5 ml, and （4） NO（group MNO, n = 10） ： i. p. Escherichia coli at 5×10^9 cfu/ml followed by iNO at 10 parts per million after ALl. Blood viscosity, malondialdehyde（MDA） in erythrocyte, Ca^2＋-Mg^2＋-ATPase and Na^＋ -K^＋-ATPase of erythrocyte membrane were measured at baseline, establishment of ALI, 12 and 24 h during the treatment. Results For normal age-matched piglets, there was little change of whole blood viscosity at high shear rate（110 s-1）, which is a measure of erythrocyte deformability, so was the level of MDA in erythrocyte and the activity of erythrocyte membrane Ca^2＋-Mg^2＋-ATPase, Na^＋-K^＋-ATPase when iNO was provided for 12 or 24 h. At the time ALl was established, whole blood viscosity at high shear rate and MDA levels in erythrocyte increased significantly compared to the baseline level（P〈 0.05）, while the activity of erythrocyte membrane Ca^2＋ -Mg^2＋ -ATPase and Na^＋-K^＋ -ATPase decreased significantly（P〈0.01, vs baseline）. Exposure of iNO for 12 h resulted in decreased whole blood viscosity at high shear rate and MDA levels in erythrocyte （P〈0.05, vs group C）, and higher activity of erythrocyte membrane Ca^2＋-Mg^2＋-AT- Pase and Na^＋-K^＋-ATPase. When iNO was administered for 24 h, there was little difference of whole blood viscosity, activity of erythrocyte membrane Ca^2＋ -Mg^2＋ -ATPase, Na^＋-K^＋-ATPase and MDA levels in erythrocyte between the C and NO groups. Conclusion In the piglets with septic ALl, there was deterioration of erythrocyte deformability. Inhaled NO for 12 h may alter the deterioration, however, this effect is transient.