姜黄素对600mL／L氧致新生大鼠肺损伤保护作用的探讨

Effect of Curcumin on Bronchopulmonary Dysplasia Induced by 600 mL/L Oxygen in Neonatal Rats

目的观察姜黄素对支气管肺发育不良(BPD)大鼠模型的干预作用,探讨姜黄素对BPD的可能保护机制。方法足月新生SD大鼠108只随机分为3组:正常对照组;600mL/L O2处理组;姜黄素干预组。于实验的第4、7、14d每组随机处死8只,HE染色观察肺组织病理结构改变;ELISA法检测血清和肺组织匀浆白介素(IL)-6、IL-10的表达;免疫组织化学法检测肺组织胰岛素样生长因子-Ⅰ(IGF-Ⅰ)蛋白的表达。结果肺组织形态学改变显示600mL/L O2处理组随着氧气暴露时间的延长,出现肺发育受阻表现,部分肺泡间隔变薄,肺泡大而简单化,而姜黄素干预组病理改变较600mL/L O2处理组改善;与正常对照组比较,600mL/L O2处理组和姜黄素干预组血清和肺组织匀浆IL-6和IL-10的表达均增高(P<0.05);姜黄素干预组IL-6的表达较600mL/L O2处理组下降,而IL-10的表达则上升(P<0.05);第4、7d时IGF-Ⅰ的表达在正常对照组中高于600mL/L O2处理组,第14d时低于600mL/L O2处理组,而姜黄素干预能增加BPD肺组织IGF-Ⅰ在第4、7d的表达(P<0.05),降低其在第14d的表达(P<0.05)。结论姜黄素可通过调控IL-6、IL-10和IGF-Ⅰ的合理表达部分逆转高氧引发的肺发育阻滞。

Objective To investigate the protective effects and potential mechanism of curcumin on bronchopulmonary dysplasis （BPD） induced by 600 mL/L oxygen in newborn rats. Methods 108 Sprague-Dawley （SD） specific pathogen-free newborn rats within 6 h after birth were randomly divided into room air group （RA group）, 600 mL/I. oxygen group （02 group） and 600 mL/L oxygen＋Curcumin group （Oz ＋Cu group）. Eight rats were randomly taken from each group and killed at 4, 7 and 14 d, respectively, after the treatment, and their lung tissues were incised for HE staining. The expressions of IL-6. IL-10 in serum and hung tissue were detected by ELISA~ and the protein expression of IGF-I was measured by immunohistoehemical method. Results Comparing with the RA group, we found that newborn rats exposed to 600 mL/L oxygen develop a heterogeneous parenchymal lung injury with areas of arrested alveolarization and growth mixed with areas of interstitial thinning, meanwhile, both the expression of IL-6 and IL-10 in serum and lung tissue increased significantly （P〈0.05）. However, in O2 ＋Cu group, IL-6 expression was decreased in different degrees while IL-10 increased significantly （P〈0.05）. The highest expression level of IGF- I in RA group were much higher from 4 d to 7 d （alveolar development period） but significantly lower in 14 d. There was a positive correlation between IGF-I and alveolar development. In comparison with RA group, the expression levels of IGF- I in 02 group were significantly lower in 4 d and 7 d but were significantly higher in 14 d （P〈0.05） ; In comparison with O2 group, the expression levels of IGF- I in O2 group significantly increased in 4 d and 7 d but significantly reduced in 14 d （P〈0.05）. Conclusion Cureumin may partly prevent the lung injury induced by prolonged hyperoxia exposure in neonatal rats probably via modulating the expressions of IL-6, IL-10 and IGF- I in serum and lung tissue.