促红细胞生成素对新生大鼠高氧肺损伤细胞凋亡的影响
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Effect of erythropoietin on apoptosis following hyperoxic lung injury in neonatal rats
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    目的:探讨人重组促红细胞生成素(rhEPO)对新生大鼠高氧肺损伤细胞凋亡的影响。方法:96只新生Sprague-Dawley大鼠随机分为4组:空气+生理盐水(NS)组,空气+rhEPO组,高氧+NS组,高氧+rhEPO组。后两组暴露于95%氧气中,高氧+rhEPO组于高氧暴露后2 d、4 d、6 d给予rhEPO 800 U /kg皮下注射, 空气+rhEPO组于同样时间点给予等量rhEPO。各组氧暴露后第3、7、14天随机抽取8只大鼠处死并取肺组织,苏木精-伊红染色观察病理变化,蛋白印迹法测定p-JNK水平,TUNEL法测定细胞凋亡。结果:与空气+NS组比较,高氧+NS组3 d出现肺泡炎性反应渗出,7 d更为明显,14 d出现肺泡数量减少,大小不均,肺大泡形成,高氧+rhEPO组的病理改变减轻,炎性反应细胞浸润减少。高氧+rhEPO组肺组织p-JNK水平较高氧+NS组有所减少,细胞凋亡减轻。结论:促红细胞生成素能通过减少细胞凋亡对新生大鼠高氧肺损伤起保护作用,其作用可能是通过JNK途径所介导。[中国当代儿科杂志,2010,12(7):576-579]

    Abstract:

    OBJECTIVE: To study the effect of recombinant human erythropoietin (rhEPO) on apoptosis following hyperoxic lung injury in neonatal rats. METHODS: Ninety-six neonatal Sprague-Dawley rats were randomly divided into four groups: air-exposed control, air-exposed rhEPO-treated, hyperoxia-exposed placebo (95% oxygen), and hyperoxia-exposed rhEPO-treated. rhEPO (800 U/kg) was administered 2, 4, and 6 days after air or hyperoxia exposure. The rats were sacrificed 3, 7 and 14 days after air or hyperoxia exposure for the assessment of lung histological changes by hematoxylin and eosin staining (n=8 each time point). P-JNK levels were measured by Western blot. Lung cell apoptosis was evaluated by TUNEL assay. RESULTS: Compared with the air-exposed control group, inflammatory cell infiltration was found at 3 days and increased obviously at 7 days, and widening of the alveolar septa was observed, the number of alveoli decreased and normal alveolarization disappeared at 14 days after hyperoxia exposure in the hyperoxia-exposed placebo group. rhEPO treatment alleviated significantly the hyeroxia-induced alterations in lung pathology. P-JNK protein levels and the number of apoptosis cells decreased significantly in the hyperoxia-exposed rhEPO-treated compared with those in the hyperoxia-exposed placebo group. CONCLUSIONS: rhEPO may reduce apoptosis and thus provide a protective effect against hyperoxic lung injury in neonatal rats. JNK signal pathway may be involved in the protective mechanism. [Chin J Contemp Pediatr, 2010, 12 (7):576-579]

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丁璐, 吴本清, 黄进洁, 刘智屏, 陈丽.促红细胞生成素对新生大鼠高氧肺损伤细胞凋亡的影响[J].中国当代儿科杂志,2010,12(07):576-579

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