高氧致肺损伤大鼠TGF-β1和MMPs基因表达的变化

Expression change of TGF-β1 and MMPs in rats with hyperoxia-induced lung injury

目的:探讨TGF-β1和MMPs的基因表达在高氧性肺损伤中的动态变化。方法:幼年Wistar大鼠32只随机分为空气对照组和高氧组(3天组、7天组、14天组),每组8只,高氧组持续吸入高浓度氧(O2>95%),用逆转录聚合酶链反应(Reverse transcript polymerse chain reaction,RT-PCR)对不同高氧暴露时间大鼠肺组织中TGF-β1、MMP-2和MMP-9的mRNA表达情况进行动态观察,并对支气管肺泡灌洗液(BALF)中蛋白含量、肺通透系数,肺湿/干重比及肺组织病理变化进行检测。结果:高氧组TGF-β1的mRNA水平从第3天开始升高,随暴露时间延长逐渐上升,到第14天仍持续不降;MMP-2、MMP-9mRNA水平从第3天也明显增加,第7天达高峰,但14天已开始下降。与之相应的肺组织病理改变为早期的急性肺泡炎和后期纤维化改变。结论:高氧致肺损伤后TGF-β1/MMPs的失衡可能是高氧性肺损伤肺纤维化发生的重要原因。

Objective：To investigate the dynamic gene expression of TGF-β1 and MMPsmRNA in pup rats with hyperoxia-induced lung injury.Methods.Thirty-two Wistar rats about two weeks were randomly divided into room-air group and hyperoxia groups（3-day group,7-day group and 14-day group）,with 8 rats in each group.After continuous exposure to high concentration oxygen（O2〉95%）,the dynamic expressions of TGF-β1 ,MMP-2 and MMP-9mRNA in lung for each hyperoxia group were measured by reverse transcript polymerse chain reaction （RT-PCR）.The protein content in bronchoalveolar lavage fluid（BALF）,permeability index,lung wet/dry weight ratio and pathological changes of lung tissues were all tested.Results：The level of TGF-β1 mRNA in hyperoxia group increased from the 3rd day,and rose gradually until the 14th day.The expressions of MMP-2 and MMP-9 mRNA increased markedly from the 3rd day,rose to the peak at the 7th day,and decreased at the 14th day.The above changes accompanied with lung pathological manifestations,which included acute alveolitis during the earlier period and lung fibrosis during later period.Conclusions：The unbalance between TGF-β1 and MMPs may play an important role in the development of lung fibrosis caused by hyperoxia-induced lung injury.