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目的 观察Notch信号在高氧暴露下新生大鼠肺组织中的表达 ,探讨其在新生大鼠高氧肺损伤发生、发展中的可能作用。 方法 将足月SD新生大鼠 4 8只随机分为对照组 ( 2 4只 ,正常空气中 )和高氧组 ( 2 4只 ,暴露于常压高氧舱中 ,氧浓度 >85 % )。高氧组高氧暴露 1、7、14、2 1d行肺组织病理学检查 ,采用免疫组化法检测Notch1 3 及其配体Jagged在肺组织中的表达 ;RT PCR半定量分析各组肺组织Notch1 3 及JaggedmRNA表达强度。 结果 与对照组比较 ,高氧组肺组织明显水肿、出血和肺发育滞后。高氧组各时间点肺组织Notch1,2 和Jagged蛋白的表达均低于对照组 (P <0 .0 5、P <0 .0 1) ,Notch3 则表达上调 ,表达主要分布于气道上皮细胞、肺泡上皮细胞、内皮细胞和成纤维细胞。高氧组NotchmRNA表达及活性均较对照组呈动态下降 (P <0 .0 1)。 结论 高氧暴露导致新生大鼠的Notch受体 /配体异常表达 ,参与了高氧肺损伤。长期暴露于 85 %的氧中 ,Notch1基因表达的向下调节可能是机体的一种保护性应激反应 ,是促进肺泡Ⅱ型细胞分化增殖的主要机制之一。Notch3 活性上调可能是高氧导致新生大鼠肺发育阻滞的重要因素
Objective To observe the expression of Notch signal in the lung tissue of neonatal rats exposed to hyperoxia and explore its possible role in the occurrence and development of hyperoxic lung injury in neonatal rats. Methods Forty eight full-term neonatal SD rats were randomly divided into control group (24 normal air) and hyperoxia group (24 exposed to normobaric hyperoxia chamber with oxygen concentration> 85%). The rats in hyperoxia group were exposed to hyperoxia for 1, 7, 14 and 21 days. The expression of Notch1 3 and its ligand Jagged was detected by immunohistochemical method. Semiquantitative RT-PCR analysis of lung tissues Notch1 3 and Jagged mRNA expression intensity. Results Compared with the control group, the lung tissue in the hyperoxia group had obvious edema, hemorrhage and delayed lung development. The expression of Notch1, 2 and Jagged protein in lung tissues in the hyperoxia group was lower than that in the control group at each time point (P <0.05, P <0.01), Notch3 was up-regulated, and the expression was mainly distributed in airway epithelial cells Alveolar epithelial cells, endothelial cells and fibroblasts. The expression and activity of Notch mRNA in hyperoxia group were significantly lower than those in control group (P <0.01). Conclusion Hyperoxia exposure leads to aberrant expression of Notch receptor / ligand in neonatal rats and is involved in hyperoxia-induced lung injury. Long-term exposure to 85% oxygen, downregulation of Notch1 gene expression may be the body’s protective stress response, is to promote alveolar type Ⅱ cell proliferation and proliferation of one of the main mechanisms. The upregulation of Notch3 may be an important factor in hyperoxia-induced lung development retardation in neonatal rats