U74389G对高氧暴露新生大鼠肺内巨噬细胞聚集和肺发育的影响  

Effects of U74389G on pulmonary macrophage influx and lung development in 95% O_2 exposed newborn rats

作　　者：罗小平[1] 廖玲洁[1] 李玉祥[1] 刘艳[1] 刘皖君[1] A. Keith Tanswell 宁琴[1] 

机构地区：[1]武汉华中科技大学同济医学院附属同济医院儿科,430030 [2]加拿大多伦多大学医学院儿科

出　　处：《中华儿科杂志》2004年第2期134-138,F003,共6页Chinese Journal of Pediatrics

基　　金：国家自然科学基金 (3 0 2 713 79) ;国家杰出青年科学基金 (3 0 12 5 0 19;3 0 2 2 5 0 40 )

摘　　要：目的　观察抗氧化剂—U74 389G对高氧暴露新生大鼠肺内自由基产物、巨噬细胞聚集、硝基酪氨酸形成以及肺细胞增殖活性的影响 ,研究高氧性肺损伤发生机制及各种介质的相互关系 ,探讨抗氧化干预的作用。方法　采用SpragueDawley新生大鼠 95 %O2 暴露 7d建立急性高氧肺损伤模型。应用气相色谱 质谱联用技术测定肺组织羟自由基 ,酶联免疫法测定脂质过氧化产物 8 异前列腺烷 ,免疫组织化学法测定肺内巨噬细胞聚集和硝基化酪氨酸形成 ,3 H TdR掺入法 (放射自显影 )测定肺细胞增殖状况。结果　 95 %高浓度氧暴露可致新生大鼠严重肺损伤 ,肺组织羟自由基(2 ,3 DHBA与 2 ,5 DHBA分别为 4 9 2± 3 5 pmol/mg、5 5 8± 2 3pmol/mg)及脂质过氧化产物 (8 异前列腺烷含量为 5 4 6 6± 32 2 pg/mg)与空气对照组比较均显著增加 (P <0 0 5 ) ,肺内巨噬细胞聚集明显 ,蛋白质酪氨酸发生显著硝基化 ,肺上皮细胞增殖停滞。抗氧化剂U74 389G可降低肺组织自由基及其衍生物产生 (2 ,3 DHBA、2 ,5 DHBA与 8 异前列腺烷水平分别为 37 9± 2 4pmol/mg、31 3±1 9pmol/mg和 35 8 5± 2 4 1pg/mg ,P <0 0 5 ) ,减少巨噬细胞聚集和蛋白质硝基化 ,肺上皮细胞增殖部分恢复 ,但未能显著改善高氧所致的肺实质病理?Objective Oxygen toxicity is believed to play a critical role in the pathogenesis of bronchopulmonary dysplasia (BPD). U74389G, a potent 21-aminosteroid antioxidant, was applied to the 95% O_2 induced acute lung injury in newborn rat model. The present study aimed to investigate the mechanism of hyperoxic lung injury and the interaction of possible mediators, and to explore the effect of antioxidant intervention. Methods Newborn Sprague-Dawley rats were randomly divided into four groups: air-exposed control, air-exposed treated with U74389G, hyperoxia-exposed control, hyperoxia-exposed treated with U74389G. Hydroxyl radical formation (2,3-DHBA and 2,5-DHBA) was assessed by an aromatic hydroxylation assay using GC/MS with salicylate as the probe. The 8-isoprostane, a specific marker for in vivo lipid peroxidation, was quantitated by enzyme immunoassay. Pulmonary macrophage influx and nitrotyrosine formation were measured by means of immunohistochemistry. 3H-TdR (autoradiography) incorporation was assessed as an index of active lung cell growth. Results Exposure to 95% O_2 for 7 days induced significant lung injury and mortality. The contents of hydroxyl radical in the hyperoxia-exposed lungs were dramatically increased [(2,3-DHBA 49.2±3.5 pmol/mg), (2,5-DHBA 55.8±2.3 pmol/mg), P <0.05) and were decreased by treatment with U74389G [(2,3-DHBA 37.9±2.4 pmol/mg), (2,5-DHBA 31.3±1.9 pmol/mg), P <0.05). The level of 8-isoprostane in the lungs of 95% O_2-exposed newborn rats was significantly raised (546.6±32.2 pg/mg, P <0.05)and lowered down by U74389G (358.5±24.1 pg/mg, P <0.05). This phenomenon was also observed in the air-exposed animals. Remarkable pulmonary macrophage infiltration was evident in hyperoxia-exposed newborn rats and was attenuated by U74389G treatment. Nitrotyrosine distributed in the lung parenchyma and epithelial cells of large airway of hyperoxia-exposed newborn rats. The extent of protein nitration was reduced by U74389G, but the oxygen induced morphological change was not significantly im

关 键 词：U74389G 高氧暴露 新生大鼠 肺内巨噬细胞聚集 肺发育 细胞增殖活性 肺损伤 

分 类 号：R722.1[医药卫生—儿科]