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目的观察高氧暴露下早产新生大鼠肺组织中的转录因子NF-E2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)和细胞色素C(Cytochrome C,Cytc)的动态表达,探讨Nrf2和Cytc的表达变化在高氧肺损伤中的作用。方法早产新生SD大鼠生后1 d随机分为两组:空气组与高氧组。空气组早产鼠置于同一室常压空气中;高氧组早产鼠持续暴露于常压氧舱中,氧质量浓度>85%。两组分别于空气或高浓度氧暴露后1、4、7、10、14 d提取肺组织标本。采用石蜡包埋切片行苏木精-伊红染色(hematoxylin-eosin staining,HE)观察肺组织的病理学变化。采取半定量逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)测定Nrf2和Cytc mRNA水平的动态表达。结果①与空气组相比较,高氧暴露4、7 d早产鼠肺组织中Nrf2 mRNA表达显著增强,10 d出现下降趋势,14 d明显减弱(P<0.05)。②与空气组相比,高氧暴露1、4 d早产鼠肺组织中Cytc mRNA均显著增强(P<0.05),7 d始出现下降趋势,但7d Cytc mRNA的表达仍稍增强、10 d时减弱,7、10 d时两者相比差异无统计学意义(P>0.05),14 d显著减弱(P<0.05)。结论氧化爆发可诱导肺组织中Nrf2与Cytc的异常表达,高氧暴露可能通过上调Nrf2活性,提高机体抗氧化,在减轻高氧肺损伤过程中发挥一定抗氧化作用;Cytc在高氧肺损伤细胞凋亡发生发展中起重要作用。
Objective To observe the dynamic expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and cytochrome C (Cytc) in the lung tissue of neonatal rats with premature neonatal exposure to hyperoxia Role of Nrf2 and Cytc expression in hyperoxia - induced lung injury. Methods The premature newborn SD rats were randomly divided into two groups one day after birth: air group and hyperoxia group. The premature rats in the air group were placed in the same room air at atmospheric pressure. The premature rats in the hyperoxia group were continuously exposed to the atmospheric oxygen chamber with oxygen concentration> 85%. The two groups were respectively taken lung tissue samples at 1, 4, 7, 10 and 14 days after air or high oxygen exposure. Paraffin-embedded sections were used to observe the pathological changes of lung tissue by hematoxylin-eosin staining (HE). Dynamic expression of Nrf2 and Cytc mRNA levels were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results ① Compared with the air group, the expression of Nrf2 mRNA in the lung tissue of premature rats exposed to hyperoxia for 4 and 7 d increased significantly, and decreased on the 10th and 14th days (P <0.05). ② Compared with the air group, the Cytc mRNA in the lung tissue of the premature rats exposed to hyperoxia for 1 and 4 days increased significantly (P <0.05), and decreased gradually on the 7th day, while the expression of Cytc mRNA remained slightly elevated on the 7th day. There was no significant difference between the two groups on the 7th and 10th day (P> 0.05), and on the 14th day (P <0.05). Conclusions Oxidative burst can induce the abnormal expression of Nrf2 and Cytc in lung tissue. Hyperoxia exposure may play an anti-oxidant role in up-regulation of Nrf2 activity and anti-oxidative activity in hyperoxia-induced lung injury. Apoptosis and development play an important role.