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高氧环境下肺成纤维细胞RB蛋白磷酸化状态的改变

赵诗萌1,魏兵2,吴红敏2,薛辛东2   

  1. 1. 中国医科大学附属第一医院新生儿科
    2.
  • 收稿日期:2011-01-27 修回日期:2011-05-05 出版日期:2011-08-15 发布日期:2011-08-15
  • 通讯作者: 赵诗萌

Variation of RB phosphorylation in lung fibroblasts of neonatal rats treated with hyperoxia

  • Received:2011-01-27 Revised:2011-05-05 Published:2011-08-15 Online:2011-08-15

摘要: 目的 探讨新生大鼠在高氧环境下肺成纤维细胞(Lung Fibroblasts, LF) RB 蛋白磷酸化状态的改变。方法 足月新生SD大鼠于生后12小时内分别持续吸入85%高氧和空气,于3、7、14、21天随机处死后动物,无菌条件下采集肺组织,进行LF细胞的原代培养, 应用免疫组化分别检测总RB蛋白及磷酸化RB蛋白(p-RB ser-795)表达。结果 高氧组与空气组相比,LF的总RB蛋白表达无明显差异(p>0.05),生后7d时高氧组p-RB蛋白表达增加(p<0.05),14d、21d时明显增加(p<0.01)。结论 高氧可能通过肺成纤维细胞P16基因表达失活,导致RB蛋白磷酸化(Rb灭活),LF过度增殖最终导致肺间质纤维化。

关键词: 高氧, 早产儿慢性肺疾病, RB蛋白磷酸化, 肺成纤维细胞

Abstract: Objective To explore the variation of RB (retinoblastoma, RB ) phosphorylation in lung fibroblasts of neonatal rats treated with hyperoxia.. Methods In 12 hours after birth, full-term newborn rats were continuously exposed to oxygen (0.85) or room air. Pups were randomly selected to be sacrificed on postnatal 3d, 7d, 14d and 21d, lungs were immediately resected under sterile condition and primary cell culture were done. the protein expressions of RB and phosphorylated RB(p-RB, ser-795) were detected by immunohistochemistry. Results Exposure neonatal rats in hyperoxia for 3 days did not change the expression of p-RB in lung fibroblast.(p>0.05). However, the expression of p-RB in hyperoxia groups was significant upregulated on 7day, 14day and 21day compared with that in air-exposed groups(p<0.05 on 7 day, p<0.01 on 14day and 21day). No notable difference was observed in the expression of RB between hyperoxia groups and air-exposed groups. Conclusion Exposure of neonatal rats in hyperoxia can down-regulate expression of P16 gene, change the phosphorylation of RB protein, ultimately lead the pulmonary interstitial fibrosis.

Key words: hyperoxia, chronic lung disease, RB phosphorylation, lung fibrolast.