吸入一氧化氮对胎粪吸入综合征新生猪一氧化氮合酶的影响

The Effect of INO Therapy on NOS in Piglet Suffered from Meconium Aspiration Syndrome

目的 观察吸入一氧化氮 (NO)治疗胎粪吸入综合征 (MAS)的疗效 ,对 MAS新生猪肺组织一氧化氮合酶 (NOS)活性的影响。 方法 建立新生猪重症 MAS动物模型 ,观察氧合 -循环变化 ,测定肺组织匀浆单磷酸环鸟苷酸 (c GMP)含量、NOS活性 ,肺组织切片原位杂交观察诱生型一氧化氮合酶 (i NOS)基因表达的变化。 结果 吸入 NO治疗使重症 MAS时的氧合 -循环障碍迅速改善 ,终止吸入 NO后肺动脉压回升至治疗前水平。MAS组肺组织原生型一氧化氮合酶 (c NOS)活性较对照组升高 (P>0 .0 5 ) ,i NOS活性较对照组显著升高 ,分别为 (16 .9± 3.1) fmol/ (m g Pro.m in)与 (11.6± 2 .7) fmol/ (mg Pro.m in) ,(P<0 .0 5 ) ,i NOS基因表达明显增强 ;吸入 NO抑制 c NOS活性 (P<0 .0 5 ) ,不能迅速 (2 h内 )抑制 i NOS的基因表达及其活性 (P>0 .0 5 )。 结论 采用逐步减量方式终止吸入 NO治疗 ,以便 c NOS活性恢复 ,避免“肺动脉压反跳现象”;及早采用包括吸入 NO在内的综合治疗措施 ,才能迅速抑制重症 MAS的肺实质炎症及 i

Objective To observe the effect of inhaled nitric oxide(INO) on the nitric oxide synthase (NOS) in piglet suffered from severe meconium aspiration syndrome(MAS). Methods Severe MAS model of piglet was reproduced, the oxygenation effect and the activity of pulmonary NOS were measured, hybridization in situ of pulmonary slices was used to show the gene expression of inducible NOS(iNOS). Results INO therapy attenuated respiratory dysfunction in MAS, while discontinuation of INO induced “rebound pulmonary hypertension”. The activity of iNOS in MAS group is higher than that in control group (16.9±3.1) fmol/(mg Pro·min)vs (11.6±2.7) fmol/(mg Pro·min),( P <0.05).The pulmonary iNOS's gene expression was enhanced by meconium and inflammatory factors, resulting in deterioration of the pulmonary inflammation. INO inhibited the activity of constitutive NOS(cNOS)( P <0.05), but the activity of iNOS and its gene expression couldn't be attenuated by INO. Conclusion INO should be withdrawn progressively to avoid “rebound pulmonary hypertension”. INO couldn't retard the pulmonary inflammation of the MAS. Simple INO therapy for MAS is not enough, other therapeutic strategies, including antiinflammation, should be adopted simultaneously when rescuing the severe MAS.