Nrf2激活对新生大鼠高氧致肺损伤的保护作用

Protective Effect of Activated Nrf2 against Hyperoxia-induced Lung Injury in Neonatal Rats

中文关键词:  高氧肺损伤 NF-E2相关因子2 新生大鼠

英文关键词:Hyperoxia lung injury Nuclear factor erythroid 2-related factor 2 Neonatal rats

中文摘要:

      目的 观察NF-E2相关因子2（Nrf2）激动剂对高氧致新生大鼠肺组织细胞凋亡的影响，探讨Nrf2激活是否对高氧致新生大鼠肺损伤具有保护作用。方法 将足月顺产SD 新生大鼠90只随机分为空气对照组( N组)、高氧组( O 组)和Nrf2组，每组各30只。O 组和Nrf2组新生鼠于出生后第1 d、第2 d分别腹腔注射生理盐水0.2 mL或Nrf2激动剂莱菔硫烷0.2 mL（30 mg/kg），N组不予任何干预。O组和Nrf2组新生大鼠于第1次注射后置入氧体积分数>95%的高氧环境中持续饲养4 d，N组则持续于空气中饲养。3组新生大鼠麻醉后取肺组织，采用TUNEL染色比较3组新生大鼠肺泡细胞的凋亡指数(AI)，采用免疫组化染色检测Nfr2在肺组织中的表达。结果 O组新生大鼠肺泡细胞AI值〔(28.8±3.0)%〕高于N组〔(0.7±0.6)%〕和Nrf2组〔(7.2±0.8)%〕，差异有统计学意义（P<0.01）。O组(926.80±130.51)和Nrf2组(1 038.40±151.12)肺组织Nrf2表达差异无统计学意义（P>0.05)，但与N组(30.03±9.99)比较均明显增高，差异有统计学意义（P<0.01）。结论 Nrf2激动剂可减少高氧致新生大鼠肺泡细胞凋亡，对高氧引起的肺损伤具有一定的保护作用。

英文摘要:

      Objective To observe the effect of nuclear factor erythroid 2-related factor 2 （Nrf2） agonist on the apoptosis of alveolar cell induced by hyperoxia and to explore whether Nrf2 activation could protect neonatal rats from hyperoxia induced lung injury. Methods 90 neonatal Sprague-Dawley rats were randomized into room air group (FiO₂ =21%, N group), hyperoxia group (O group) and Nrf2 group (n=30 each).Neonatal rats in the O group and Nrf2 group received saline 0.2 mL and Nrf2 agonist 30 mg/kg respectively at the first and second day after birth, and were exposed in high concentration oxygen (95%) for 4 d. N group rats were fed in room air. The apoptotic index (AI)and Nrf2 expression of lung tissue were detected by TUNEL and immunohistochemistry staining respectively. Results Compared with O group (28.8%±3.0%), the AI of alveolar cell was lower in N group (0.7%±0.6%) and Nrf2 group (7.2%±0.8%)（P<0.01）. The expression of Nrf2 was significantly higher in O group (926.80±130.51) and Nrf2 group (1 038.40±151.12) than that in N group (30.03±9.99)（P<0.01）. Conclusion Nrf2 activation could reduce the alveolar cellular apoptosis and protect neonatal rats from hyperoxia induced lung injury.