乌司他丁上调水通道蛋白1保护新生猪体外循环肺缺血/再灌注损伤

目的探讨乌司他丁对新生猪体外循环肺缺血/再灌注后的保护作用以及水通道蛋白1(aquaporin 1,AQP1)在此病理过程中的表达。方法 12只健康新生猪依据主动脉开放前是否通过肺动脉注射乌司他丁,随机分为两组:对照组(control,n=6)和实验组(test,n=6),实验组在主动脉开放前通过肺动脉注射乌司他丁10 000 U.kg-1(0.154 mol.L-1生理盐水稀释至30 ml)。在开胸后即刻(T1)、主动脉开放90 min实验结束前(T2)留取肺泡灌洗液、肺组织标本和肺静脉血标本。光镜观察并盲法评分比较肺组织病理学变化;检测肺泡灌洗液中性粒细胞(PMN)计数;酶联免疫吸附法检测肺静脉血清白介素6(IL-6)和肿瘤坏死因子α(TNF-α)含量;肺组织湿干重比(wet/dry weight,W/D);免疫组化和Western blot检测肺组织AQP1表达。结果两组相比,实验组肺组织病理变化明显减轻;肺泡灌洗液中性粒细胞(PMN)计数、IL-6、TNF-α和肺组织湿干重比明显降低以及AQP1表达明显提高(P<0.05)。结论乌司他丁对新生猪体外循环肺缺血/再灌注损伤具有一定的保护作用,可能的作用机制与其促进AQP1蛋白表达有关。

Ulinastatin protects the lung against ischemia-reperfusion injury with CPB by upregulating the expression of pulmonary aquaporin 1 in neonatal pig

Aim To observe the lung protection and expression of pulmonary aquaporin 1(AQP1) by ulinastatin following ischemia-reperfusion during CPB in neonat pig.Methods Twelve neonatal pigs were randomized into two groups: control group(n=6) reveived normal cardiopulmonary bypass;test group(n=6) received ulinastatin by pulmonary artery.Lung injuries,which was marked by pulmonary pathology,PMN in BALF,IL-6 and TNF-α in pulmonary vein and pulmonary wet/dry weight(W/D) were analyzed.Expression of aquaporin 1 were analyzed by immunohistochemistry and Western blot.Results Compared with control group,pathological scores,PMN in BALF,IL-6,TNF-α and W/D in test group at T2 were significantly lower(P<0.05).Expression of AQP1 in test group increased significantly at T2(P<0.05).Conclusions Ulinastatin is protective on the lung ischemia-reperfusion injury with CPB in neonatal pig.The protective effects were related with its upregulation of aquaporin 1.