高氧诱导新生鼠急性肺损伤模型的制备及其机制探讨  

Preparation and possible mechanisms of the model of oxygen-induced acute lung injury in neonatal rats

作　　者：潘佳容[1] 肖志辉[2] 张晨美[1] 

机构地区：[1]浙江大学医学院附属儿童医院急诊科,浙江杭州310003 [2]苏州大学附属儿童医院新生儿科

出　　处：《全科医学临床与教育》2008年第2期135-137,F0002,共4页Clinical Education of General Practice

摘　　要：目的建立新生儿高氧急性肺损伤的动物模型,并探讨其发病机制。方法采用新生Sprague-Dawley(SD)大鼠持续暴露于90%～95%的常压氧气造成高氧急性肺损伤。实验3、7d时分别检测高氧模型组和对照组支气管肺泡灌洗液(BALF)中丙二醛(MDA)、超氧化物岐化酶(SOD)、肿瘤坏死因子-α(TNF-α),测定肺组织核因子-κB(NF-κB)染色强度,并观察肺组织病理表现。结果与对照组比,高氧组3d时BALF中MDA、TNF-α含量升高(t分别=7.07、6.45,P均<0.05),SOD活性下降(t=4.56,P<0.05),肺组织NF-κB活性上升(t=50.08,P<0.05),肺组织见小血管扩张、充血和肺泡内少量出血及以中性粒细胞、巨噬细胞为主的炎性细胞浸润;7d时,高氧组BALF中MDA、TNF-α含量进一步升高(t分别=9.70、7.20,P均<0.05),SOD活性进一步下降(t=7.15,P<0.05),NF-κB染色强度进一步升高(t=98.05,P<0.05),肺组织充血、水肿,间质内浸润的中性粒细胞、巨噬细胞等增多,肺泡间隔轻度增宽,肺组织结构紊乱。结论新生鼠持续暴露于高浓度氧气可制备新生儿高氧急性肺损伤动物模型。高浓度氧致脂质过氧化,抗氧化酶系统活性降低,NF-κB过度活化,TNF-α过度释放,氧化/抗氧化系统失衡和过度炎症反应是肺损伤的重要发病机理。Objective To establish an optimal animal model of oxygen-induced acute lung injury （ALI） in neonate,and to study the possible underlying mechanism. Methods Persistence exposure of 90%-95% oxygen resulting in ALl was practiced in neonatal Sprague-Dawley（SD） rats. At the third day and seventh day of exposure, malondialdehyde （MDA） ,superoxide dismutase （SOD） and TNF-αin bronchoalveolar lavage fluid （BALF） were determined and the intension of nuclear factor -κB （NF -κB） expression in rat lung was analyzed by the method of immunohistochemistry,and lung histopathological changes were examined in hyperoxic group and control group. Results After 3 days, compared with the control group,hyperoxic group showed ALI characterized by the increase in the concentration of MDA , TNF-α in BALF and the intension of NF -κB in rat lung while the decrease in the activity of SOD in BALF （t=7.07,6.45,50.08,4.56, P〈0.05） and presence of congestion, edema, inflammatory infiltration. After 7 days, continuous increase in the concentration of MDA , TNF-α in BALF and the intension of NF-κB in rat lung and continuous decrease in the activity of SOD in BALF were observed （t= 9.70,7.20,98.05,7.15, P〈0.05）, and lung histopathological presence showed more severe changes in hyperoxic group. Conclusions An optimal animal model of oxygen-induced ALl in neonate was established by persistence exposure of 90%～95% oxygen with neonatal S-D rats. Excesses of lipid peroxidation, decrease of activity of antioxidase, increase of activity of NF-κB and excess release of TNF-α are associated with hyperoxia. The mechanisms of imbalance of oxidant/antioxidant and inflammation may play important roles in the development ofhyperoxic lung injury.

关 键 词：高氧 肺损伤 疾病模型 动物 核因子-ΚB 

分 类 号：R-332[医药卫生]