吸入一氧化氮对早产猪未成熟肺的作用

Effects of inhaled nitric oxide on lung function in ventilated premature piglets

摘要:

目的：研究早产猪在机械通气下吸入一氧化氮(NO)对未成熟肺的呼吸功能、核转录因子(NFκB)表达的影响,以研究出生早期吸入NO是否对不成熟肺产生不良反应,并判断应用肺表面活性物质(PS)及NO的肺保护作用效果及其调节炎症反应的作用和机制。方法：选择101～103d孕龄(89%足月孕期)母猪,行剖宫产获得32头早产猪(平均出生体重870g),气管插管后行间歇正压机械通气,随机分成4组(每组n=8)治疗:单纯机械通气(C组);吸入NO(NO组);加用肺表面活性物质(PS组)；NO和PS联合应用(SNO组)。另选同窝自主呼吸组(N组)用于比较NFκB水平、肺湿干重比及肺组织病理学。机械通气各组分别测肺功能,血气分析,计算氧合指数(OI)和通气指数(VI)。机械通气6h后处死动物。结果：治疗6h肺顺应性(Cdyn)和气道阻力(Raw)在各组间无统计学差异,OI在SNO组显著低于C组2.3±1.9vs9.5±7.5(P<0.05),VI在NO和SNO组低于C组和PS组(P<0.05或P<0.01)。NO组及N组NFκB活性最低,与C组相比差异有显著性,P<0.05。NO吸入过程中监测NO2水平均<1ppm。所有动物高铁血红蛋白(MetHb)浓度均<4%。NO和SNO组肺组织湿干重比显著低于C组6.88±0.53vs7.77±0.76(P<0.05)和6.61±0.56vs7.77±0.76(P<0.01)。病理检查见各组不同程度肺水肿、白细胞浸润,肺泡扩张度(Vv)和变异度(CV[Vv])显示肺泡中度成熟,但差异均无显著性。结论：出生早期应用iNO或联合应用PS治疗可改善早产猪氧合和机械通气效率;小剂量短时间NO吸入有利于肺液清除,没有显著改变PS成分和/或直接致肺损伤;NO通过下调NFκB可能具有抑制/调节早产肺炎症反应启动机制的作用。

Abstract:

OBJECTIVE: To investigate the efficacy of nitric oxide (NO) inhaltion on lung function and modulation of inflammation in ventilated premature piglets. METHODS: Premature piglets were obtained at gestation of 101-103 days (89% of full term) with a mean body weight of 870 g. All animals were subjected to mechanical ventilation (PEEP 4-6 cmH2O, Vt 6-8 mL/kg, RR 40-60/min)and randomized into 4 group(n=8 each): Ventilation control, NO inhalation (5-10 ppm), Surfactant (100 mg/kg) or NO plus surfactant. Before and during the ventilation blood gas and lung mechanics were monitored. At the end of the experiment, the lung samples were taken for measuring the NF-κB activity, wet/dry weight ratio and histopathology, and the results were compared with those from 10 non-ventilated premature piglets. RESULTS: The oxygenation index was significantly lower in the NO+surfactant-treated group compared with that of the Control group (2.3±1.9 vs 9.5±7.5, P<0.05). The alveolar aeration in the lungs was similar among the treatment groups. Both NO and NO+surfactant treatments significantly improved the ventilation index. The NO-treated and the Non-ventilated groups had a significantly lower NF-κB activity and wet/dry lung weight ratio compared with the Control group. Neither methemoglobin and NO-2 levels nor inflammatory lung injury was significantly increased in the NO and combined with surfactant-treated groups. CONCLUSIONS: Early treatment with NO alone or combined with surfactant can improve oxygenation and ventilation efficacy without obvious adverse effects on immature lungs of premature piglets. The beneficial effects of NO may be due to the suppresion of NF-κB activity.