结缔组织生长因子在高氧致早产鼠慢性肺疾病中的表达及其作用

Expression and effect of connective tissue growth factor in premature rats with hyperoxia-induced chronic lung diseases

目的肺纤维化是高氧致慢性肺疾病(chroniclungdiseases,CLD)的最终结局,结缔组织生长因子(connectivetissuegrowthfactor,CTGF)是近年来发现的与纤维化形成密切相关的因子,但其在CLD肺纤维化中的作用目前尚未见报道。该实验旨在研究CTGF在高氧致CLD中的动态表达规律,并探讨其在CLD中的作用。方法将50例早产鼠随机分为实验组(高氧组)和对照组(空气组),分别于建立模型后1,3,7,14,21d应用免疫组化技术动态检测肺组织中CTGF的表达部位和强度,对肺组织纤维化程度进行病理组织学评分。结果对照组小鼠CTGF仅在血管内皮细胞、支气管、细支气管上皮细胞有微弱表达;实验组于建立模型后1,3,7d表达部位与对照组相似,表达强度与对照组无差异(P>0.05),14d表达增强(P<0.01),在部分肺上皮细胞、肺泡间隔、成纤维细胞中出现表达,21d表达明显增强(P<0.01)。高氧组14d和21dCTGF表达水平与肺组织纤维化程度呈明显正相关(分别为r=0.903,r=0.926,均P<0.01)。结论随着高氧暴露时间的延长和纤维化的发展,CTGF表达增强,其与高氧所致CLD肺纤维化的发生密切相关。

Objective Lung fibrosis is the ultimate outcome of hyperoxia-induced chronic lung diseases （CLD） and connective tissue growth factor （CTGF） is correlated with fibrosis. This study investigated the role of CTGF in hyperoxiainduced CLD. Methods Fifty premature rats were randomly exposed to hyperoxia （Model group ） and to room air （ Control group） （ n = 25 each ）. CLD was induced by hyperoxia exposure. The expression of CTGF was detected by immunohistochemical method at 1,3, 7, 14 and 21 days after exposure. The severity of pulmonary fibrosis was evaluated. Results In the Control group there was a slight expression of CTGF in the bronchial epithelial cells and vascular endothelial cells. The intensity and range of CTGF expression in the Model group were similar to the Control group on days 1, 3 and 7 of exposure. On the 14th day, CTGF was expressed in some alveolar epithelial cells, fibroblasts and interstitial cells, and the intensity of CTGF expression increased significantly compared with the Control group, with the IODT of CTGF of 10.53 ± 4.24 vs 5.58 ± 1.18 （P 〈0.01 ）. On day 21, the expression intensity and range of CTGF in the Model group （IODT： 16.61 ±5.39） increased compared with that of Control group （P 〈 0.01 ）. The expression of CTGF was correlated with the degree of fibrosis in the Model group on days 14 and 21 （ r =0. 903, r =0.926 respectively, P 〈0.01 ）. Conclusions The CTGF expression increased with the time of hyperoxia exposure and the development of fibrosis. CTGF is closely related to the development of hvDeroxia-induced pulmonary fibrosis.