吸入一氧化氮治疗对内毒素所致急性肺损伤肺泡液体清除影响的实验研究

目的 观察吸入不同浓度一氧化氮(NO)对急性肺损伤(ALI)时肺水肿形成、肺泡液体清除和渗出的影响,并探讨其治疗机制,为临床选择吸入NO(iNO)治疗ALI及其治疗方式提供理论依据.方法 健康雄性新西兰大耳白兔18只,建立内毒素脂多糖(LPS)所致肺损伤模型(0 h).将动物随机均分成3组:①机械通气(MV)组:行容积控制通气(VCV),潮气量(VT)15 ml/kg,呼气末正压(PEEP)5 cm H2O(1 cm H2O=0.098 kPa),通气频率40次/min;②高iNO(HNO)组:在MV组治疗基础上给予40×10-6 NO吸入;③低iNO(LNO)组:在MV组基础上加10×10-6 NO吸入.检测通气后不同时间点各组大鼠血流动力学、血气分析、呼吸力学等指标.通气4 h后放血处死动物,计算肺湿/干重(W/D)比值,并观察肺泡液体渗出情况.结果 ①治疗后0.5 h,HNO组和LNO组的氧合指数(PaO2/FiO2)显著高于MV组,并维持到实验结束(P均＜0.05).②治疗后0.5、2和4 h,LNO组气道峰压(Ppeak)和平台压(Pplat)较MV组下降(P＜0.05或P＜0.01);HNO组4 h时的Ppeak、2 h和4 h的Pplat低于MV组(P＜0.05或P＜0.01);LNO组2 h和4 h时的Pplat明显低于HNO组(P均＜0.01).③HNO组和LNO组肺泡液体渗出少于MV组(F=22.756,P＜0.01),肺泡液体清除多于MV组(F=3.965,P＜0.05),肺组织W/D比值MV组＞HNO组＞LNO组(F=11.740,P＜0.01).④HNO组和LNO组的肺损伤评分好于MV组,但差异无统计学意义.结论 ALI早期iNO治疗可显著促进肺泡液体清除、改善肺泡液体渗出、减轻肺水肿、改善氧合和降低气道压,相对较低浓度(10×10-6)吸入治疗可能更有益.

Nitric oxide inhalation improves alveolar liquid clearance in rabbit with endotoxin induced acute lung injury

OBJECTIVE: To investigate the effects of nitric oxide (NO) inhalation (iNO) on alveolar liquid clearance (ALC), alveolar permeability, and lung edema, and its possible mechanism. METHODS: Eighteen male rabbits were challenged with endotoxin, and they were randomly assigned into three groups: mechanical ventilator (MV) group [volume control ventilation: tidal volume (V(T)) 15 ml/kg, respiration rate (RR) 40 beats/minute, positive end-expiratory pressure (PEEP): 5 cm H(2)O (1 cm H(2)O=0.098 kPa)], high; NO ( 40 x 10(-6) NO, HNO) group and low concentration; NO (10 x 10(-6) NO, LNO) group. Indexes including haemodynamics, blood gas analysis, and mechanics of breathing were determined after MV at different time points in each group. The rabbits were sacrificed after MV lasting for 4 hours. Wet/dry weight (W/D) ratio of the lung was calculated, and the condition of alveolar exudation was observed. RESULTS: (1) Oxygenation index (PaO(2)/FiO(2)) in HNO group and LNO group were higher than those in MV group at 0.5 hour after treatment. (2) The peak pressure of airway (Ppeak) and plateau pressure of airway (Pplat) in LNO group were lower than those in MV group at 0.5, 2 and 4 hours after treatment (P<0.05 or P<0.01). Ppeak at 4 hours, Pplat at 2 hours and 4 hours were lower in HNO group as compared with those in MV group (P<0.05 or P<0.01). Pplat in LNO group was lower than that in HNO group at 2 hours and 4 hours (both P<0.01). (3) Alveolar exudation in HNO group and LNO group was milder than that in MV group (F=22.756, P<0.01). ALC in HNO group and LNO group were higher than that in MV group (F=3.965, P<0.05). The W/D ratio of lung in MV group was higher than that in HNO group, and the W/D rate in HNO group was higher than that in LNO group (F=11.740, P<0.01). (4) Lung injury score in HNO group and LNO group was higher than that in MV group, but without significant difference. CONCLUSION: iNO can reduce lung edema by increasing ALC and improving alveolar permeability, and the LNO may be more effective than HNO in treatment of early acute lung injury induced by endotoxin.