姜黄素通过抗炎机制减轻60%氧致新生鼠的肺损伤

Curcumin attenuates 60% oxygen-induced lung injury via anti-inflammatory mechanisms in neonatal rats

目的研究姜黄素对支气管肺发育不良(BPD)肺组织病理改变、肿瘤坏死因子-α(TNF-α)和胰岛素样生长因子结合蛋白-2(IGFBP-2)表达的影响。方法 144只足月新生SD大鼠随机分为4组:正常对照组、姜黄素对照组、BPD模型组、姜黄素干预组。分别于实验的第4、7、14天随机处死8只,取肺组织做HE染色,辐射状肺泡计数(RAC);检测血清和组织匀浆TNF-α、IGFBP-2的表达。结果 BPD模型组随氧气暴露时间的延长,出现炎性浸润和渗出,肺泡间隔不均匀增厚,肺泡大而简单化,较正常对照组明显发育迟滞,而姜黄素干预组病理改变较BPD模型组明显改善;与正常对照组和姜黄素对照组比较,BPD模型组血清和组织匀浆TNF-α、IGFBP-2的表达均显著增高(P<0.05),姜黄素干预后TNF-α、IGFBP-2的表达较模型组明显下降(P<0.05),正常对照组和姜黄素对照组之间无显著性差异;IGFBP-2mRNA水平与蛋白水平趋势一致。结论姜黄素可部分逆转高氧引发的肺发育阻滞,下调高氧暴露下TNF-α、IGFBP-2的表达可能是其干预肺损伤的机制之一。

This study aimed to discuss the effects of curcumin on histological changes,serum expression of TNF-α and IGFBP2,and lung tissue of 60% oxygen-induced bronchopulmonary dysplasia（BPD） in neonatal rats and its potential molecular mechanism.Total of 144 Sprague-Dawley（SD） pathogen-free term neonatal rats were randomly divided into 4 groups：room air group,room air ＋ curcumin group,60% oxygen group,60% oxygen ＋curcumin group.Eight rats were randomly taken from each group and sacrificed at 4,7 and 14 days for collecting blood and lung tissues.The histopathological changes and lung radical alveolar counts（RAC） were examined by hematoxylin and eosin（HE） staining;the mRNA of IGFBP-2 in the 1ung tissue was determined by reverse transcriptionpolymerase chain reaction（RT-PCR）;the level of TNF-α and IGFBP-2 in serum and lung tissue were detected by ELISA.We found in BPD group,erythrocyte and inflammatory cells infiltrated into the alveolar space,alveolar septum inhomogeneous thickened,and alveolar structure disordered accompanied with developmental lag when compared with the room air group and room air ＋ curcumin group,furthermore,such pathological changes aggravated with hyperoxia exposure prolong.Both the concentration of TNF-α and IGFBP-2 in serum and lung tissue increased significantly（P 0.05） in BPD groups,while decreased in different degrees after treated with curcumin（P 0.05）,but there were no significant differences between the room air group and room air ＋ curcumin group.The expression of IGFBP-2 mRNA was consistent with the change tendency of the protein in all 4 groups.Thus,curcumin may partly prevent the retardation of fetal lung development caused by prolonged hyperoxia exposure,whose potential mechanism might be that curcumin down regulates the expressions of TNF-α and IGFBP-2 in serum and lung tissue.