非肽内皮素拮抗剂在体外循环中的肺保护作用

Protective Effect of Non-peptide Endothelin Antagonist Ferulic Acid on Lung Injury During Cardiopulmonary Bypass.

目的研究体外循环(CPB)过程中内皮素(endothelin,ET)在肺损伤中的作用,探讨ET介导肺损伤的可能机制及阿魏酸(FA)对肺的保护作用。方法将12只犬随机分为两组,建立CPB肺灌注模型。对照组:灌注4℃冷晶体心脏停搏液;实验组:于肺动脉近端灌注4℃FA保护液;观察两组CPB前后肺组织内ET的浓度、一氧化氮(NO)、丙二醛(MDA)含量及肺组织干湿比(D/W)变化、氧合指数(PaO2/FiO2)、肺血管阻力(PVR)、气道压(AWP)、肺顺应性和组织学变化。结果CPB后对照组肺内ET合成显著增加(P<0.05),实验组低于对照组(P<0.05);D/W,MDA较对照组降低(P<0.05),NO含量较对照组增高(P<0.05)。CPB后实验组PaO2/FiO2、肺顺应性分别高于对照组(P<0.05),而AWP、PVR则低于对照组(P<0.05);实验组肺损伤较对照组轻。结论ET参与CPB中的肺损伤过程;用FA进行肺灌注可减轻肺损伤,改善肺功能,具有较好的肺保护作用。

Objective To investigate the role of endothelin（ET） in lung injury during cardiopulmonary bypass （CPB） and study the possible mechanism of ET-mediated lung injury and the protective effect of ferulic acid（FA） during the procedure. Methods Twelve dogs were randomly divided into 2 groups and models of CPB with pulmonary perfusion were established by perfusion of 4 C FA solution through proximal pulmonary artery in the experiment group while control group only received 4 C crystal cardiac arrest solution without pulmonary perfusion. Changes in the content of ET, NO, malonaldehyde （MDA）, dry to wet （D/W） in lung tissue and lung function- related indices PaO2/FiO2, airway pressure （AWP）, pulmonary vascular resistance （PVR）, lung compliance before and after CPB in both groups were measured respectively. Results ET content increased after CPB in control group （P〈0. 05） ,while experiment group had a lower level of ET than that of control group （P〈0.05）; D/W, MDA levels in experiment group decreased （P〈0. 05）, but NO content increased （P〈0. 05） as compared with control group. After pulmonary perfusion with FA, PaO2/FiO2 and lung compliance values in experiment group were higher than those of control group （P〈0.05）,AWP, PVR values lowered accordingly（P〈0. 05）. Lung injury was less severe in the experiment group. Conclusion ET is involved in pathogenesis of lung injury during CPB, FA can effectively reduce lung injury and improve lung function thus having a good protective effect on the lung.