CLD早产鼠肺组织内TGF -β1的动态表达及其对细胞外基质的影响(英文)

Dynamic expression and effect of TGF-β1 on extracellular matrix in premature rats with CLD

摘要:

目的 近年来发现慢性肺疾病 (CLD)早产儿支气管肺泡灌洗液中转化生长因子 β1(TGF β1)及I型胶原等细胞外基质 (ECM )水平增高 ,但由于临床研究的局限性 ,缺乏与肺组织ECM的对照研究。因此探讨TGF β1在早产鼠CLD发生、发展中的变化规律及对ECM的影响对完善早产儿CLD的发生机制有重要意义。 方法 将 6 0例早产鼠随机分为模型组和对照组 ,于实验后 1,3,7,14和 2 1d ,应用免疫组织化学和酶联免疫吸附法 ,分别观察及测定肺组织TGF β1分布、表达强度及I型胶原、纤维连接蛋白 (FN)及透明质酸 (HA)的含量。 结果 正常肺组织TGF β1仅在支气管上皮细胞或血管内皮细胞有微弱表达 ;而模型组 1d和 3d时 ,TGF β1表达同正常对照组 ,7d时少量肺泡巨噬细胞、肺泡上皮细胞及肺间质细胞开始表达 ,其表达强度高于对照组 ,差异有显著性(P <0 .0 5 ) ,14d时明显增强 ,差异有极显著性意义 (P <0 .0 1) ,2 1d达高峰 ;1,3和 7d时 ,两组肺组织I型胶原含量无差异 (P >0 .0 5 ) ,而 14d时 ,模型组高于对照组 ,差异有显著性 (P <0 .0 5 ) ,2 1d时明显高于对照组 ,差异有极显著性意义 (P <0 .0 1) ;不同吸氧时间 ,两组肺组织FN及HA含量均差异无显著性意义 (P >0 .0 5 ) ;模型组在 14d和 2 1d时 ,肺组织TGF β1表达与I型胶原含

Abstract:

Objective To investigate the effect of transforming growth factor-β1 (TGF-β1) on the extracellular matrix (ECM) of lungs in premature infants with chronic lung disease (CLD). Methods Sixty premature rats were randomly assigned into a Model group of CLD and a Control group (n=30 each). CLD was induced by hyperoxia exposure. The distribution and expression of TGF-β1 and levels of type I collagen, fibronectin (FN) and hyaluronic acid (HA) from lung specimens were assayed by the immunohistochemical method and enzyme-linked immunoabsorbent technique on days 1, 3, 7, 14 and 21 of the experiment. Results In the Control group there was a slight expression of TGF-β1 in bronchial epithelial cells and vascular endothelial cells. In the Model group, the TGF-β1 expression was similar to that of the Control group on day 1 and day 3, while on day 7, the TGF-β1 expression in alveolar macrophages, alveolar epithelial cells and interstitial cells was found. Expression intensity and range were increased with the time of hyperoxia-inducement and reached a peak on the 21st day. On days 1, 3, and 7, there were no differences in the type I collagen level between the two groups. On day 14, however, it was higher in the Model group than that of the Control group (P< 0.05). This difference was more significant on day 21 (P< 0.01). Levels of FN and HA in the Model group did not differ from those of the Control group at any time point of the experiment. The level of TGF-β1 expression was postitively correlated with the type I collagen level on day 14 (r= 0.709,P< 0.01) and day 21 (r= 0.711, P< 0.01). Conclusions Over-expression of TGF-β1 may play an important role in ECM remodeling in rats with hyperoxia-induced CLD.