洛沙坦对高氧致新生大鼠慢性肺疾病的保护作用  

Protective effect of Losartan in hyperoxia-induced chronic lung disease in newborn rats

作　　者：陈宁[1] 单丽沈[1] 尚云晓[1] 薛辛东[1] 

机构地区：[1]中国医科大学附属盛京医院小儿呼吸内科,辽宁沈阳110004

出　　处：《中国现代医学杂志》2011年第11期1302-1306,共5页China Journal of Modern Medicine

基　　金：国家自然科学基金(No:30672253)

摘　　要：目的研究血管紧张素II1型受体拮抗剂洛沙坦对高氧致新生大鼠慢性肺疾病（CLD）肺组织的影响,探讨肺组织局部肾素血管紧张素系统（RAS）在CLD发病中的可能机制。方法将Wistar新生大鼠生后24h内随机分为空气组（Ⅰ）、高氧组（Ⅱ）、高氧＋注射用水组（Ⅲ）和高氧＋洛沙坦组（Ⅳ）,Ⅱ~Ⅳ组氧浓度为85%~90%,Ⅲ、Ⅳ组在生后6 d每天用注射用水和洛沙坦（5 mg/kg）灌胃至实验结束,在实验的1、3、7、14和21 d处死,HE染色和放射性肺泡计数（RAC）观察肺组织病理改变,免疫组织化学检测α-SMA蛋白表达;生化检测羟脯氨酸（HYP）的含量。结果Ⅱ和Ⅲ组肺组织肺泡间隔显著增厚,肺泡数目减少,终末气腔扩张,RAC较Ⅰ组显著下降（P〈0.01）。Ⅳ组肺泡间隔变薄,但肺泡腔没有明显缩小,RAC仍明显低于Ⅰ组。高氧暴露后α-SMA在肺泡间隔和肺泡表面表达显著增强,呈条索状分布;Ⅱ和Ⅲ组7d后较Ⅰ组α-SMA表达显著增强（P〈0.01）;Ⅳ组α-SMA表达较Ⅱ组明显减弱,14 d较Ⅱ组明显下降（P〈0.05）,21 d时则显著下降（P〈0.01）,但仍高于Ⅰ组（P〈0.01）。高氧后14 d和21 d新生大鼠肺组织HYP含量显著增加（P〈0.01）,洛沙坦干预后能明显减轻肺纤维化的程度。结论肺局部RAS系统参与高氧CLD的发生,洛沙坦只能抑制CLD新生大鼠肺纤维化的进展,但并不能逆转高氧诱导的新生大鼠肺发育阻滞。【Objective】To investigate the effect of Losartan,an angiotensin II type 1 receptor antagonist,on newborn rats with hyperoxia-induced chronic lung disease（CLD） and Speculate the role of local renin an-giotensin systems（RAS） in the lung tissue in the pathogenesis of CLD and possible mechanisms.【Methods】 Within 24 hours after birth,neonatal Wistar rats were divided randomly into four groups： air group（I）,O2 ex-posed group（II）,O2 exposed ＋ aqua group（Ⅲ）,O2 exposed ＋ Losartan group（Ⅳ）.Except group I,neonatal Wistar rats were exposed to about 85%~90% oxygen;from the 6 d after birth to the end of experiment,thepups in group Ⅲ and Ⅳ received aqua and Losartan（5 mg/kg） by intragastric administration daily.Pups ineach group were sacrificed on 1,3,7,14 and 21 d after the birth.Lung histological changes were evaluatedby Hematoxylin eosin and radical alveolar counts（RAC）,alpha-SMA proteins were detected by immunohisto-chemistry.Hydroxyproline in lung tissues were determined by spectroscopy.【Results】Hyperoxia-exposed re-sulted in secondary septum decreased,enlarged terminal air space,and alveolar septa was thicker.RAC ingroup Ⅱ and Ⅲ decreased significantly compared to Ⅰ（P 0.01）.Alveolar septum was thinner in Ⅳ com-paring with group Ⅱ,but alveolar cavity was not deflate obviously,RAC was still lower significantly than thatin group Ⅰ.Neonatal rats exposed to hyperoxia enviorment caused alpha-SMA expression increased markedly in alveolar septa and the surface of alveolar on 14 and 21 d.After 7 d,alpha-SMA expression in group Ⅱand Ⅲ was significantly increased than in group Ⅰ（P 0.01）.Alpha-SMA in group Ⅳ decreased comparedwith group Ⅱ on 14 d（P 0.05）,on 21 d decreased significantly（P 0.01）,but still higher than group Ⅰ（P 0.01）.In group Ⅱ~Ⅲ,hydroxyproline contents in lung tissue were increased significantly on 14 and 21 days（P 0.01）.Losartan attenuated slightly the degree of lung fibrosis on 14 and apparently on 21 days.�

关 键 词：新生儿 慢性肺疾病 高氧 Α-平滑肌肌动蛋白 洛沙坦 

分 类 号：R563.1[医药卫生—呼吸系统]