乌司他丁对重度烫伤大鼠全麻中肺组织保护作用的实验研究

Ulinastatin ameliate lung damage induced by mechanical ventialtion for serious burned rats:an experimental study

目的探讨重度烫伤后麻醉时乌司他丁预处理对机械通气造成的肺组织损伤是否具有保护作用。方法 90只Wistar大鼠,随机分为3组,对照组30只,全麻组30只,乌司他丁组30只。建立大鼠重度烫伤模型后,对照组不进行机械通气,全麻组和乌司他丁组机械通气1h(乌司他丁组通气前接受乌司他丁预处理)。通过观察肺组织大体标本,HE染色观察肺部病理学改变,电镜观察组织超微结构改变,评估肺系数,免疫组织化学染色检测肺组织细胞因子TNF-α、IFN-γ、IL-2的表达水平来检测重度烫伤后,乌司他丁对机械通气造成的肺损伤是否具有保护作用。结果对照组和全麻组大鼠两肺明显水肿,可见出血灶,切面疏松、肿胀;乌司他丁组大鼠两肺充血水肿相对温和。HE染色可见乌司他丁组肺组织病变轻于全麻组。电镜下:对照组和全麻组肺组织细胞器破坏严重;乌司他丁组相应改变较轻。对比肺系数发现乌司他丁组肺系数与全麻组相比显著下降。免疫组织化学结果显示乌司他丁预处理后肺组织表达TNF-α、IL-2、IFN-γ的强度较全麻组显著降低。结论乌司他丁对重度烫伤大鼠全麻时机械通气所导致的肺损伤具有保护作用。这种保护作用可能与乌司他丁降低细胞因子TNF-α、IFN-γ、IL-2的表达水平有关。

Objective To explore the potential protective effects of ulinastatin on ventilation-induced lung injuries of severe burned rats.Methods Ninety Wistar rats were randomly divided into three experimental groups：control group（n =30）,ventilation group （n =30） and ventilation-ulinastatin group （n =30）.After establishing the severe burn model,the rats of latter two groups were mechanically ventilated for 1 hour with or without the pretreatment of ulinastatin.The lung injury was evaluated by pathological changes,lung index and the expression level of cytokines including TNF-α,IL-2,and IFN-γ at 2 hours,6 hours and 12 hours post-ventilation.The samples of lung tissue at the last time point （12 hours） were used for both HE staining and electron microscopy analysis.Results The lung tissues of the control and ventilation groups exhibited markedly pulmonary edema and scatteted hemorrhagic foci.In contrast,ventilation-ulinastatin group demonstrated milder pulmonary edema.HE staining revealed that the pathological changes of ventilation-ulinastatin group were milder than ventilation group.Under electron microscopy,severe organelle destruction was noted for the lung tissue of control group and ventilation group.In contrast,ventilation-ulinastatin group demonstrated milder pathological changes.Pulmanary index showed that the value of ventilation-ulinastatin group decreased significantly compared with ventilation group.Immunohistochemical staining demonstrated lower expression of TNF-α,IL-2,IFN-γ in ventilation-ulinastatin group compared with ventilation group.Conclusions Ulinastatin attenuated ventilation-induced lung injury in a severe bum model of rat.The protective effects of ulinastatin maybe related to the capacity of ulinastatin to reduce the expression of cytokines including TNF-α,IL-2,and IFN-γ.