重组人促红细胞生成素对宫内炎性暴露和高氧肺损伤新生大鼠细胞凋亡及PI3K表达的影响

Effect of recombinant human erythropoietin on PI3K gene expression and apoptosis in the lung of neonatal rats exposed to intraamniotic endotoxin and hyperoxia

目的探讨重组人促红细胞生成素(rhEPO)对宫内炎性暴露和高氧肺损伤新生大鼠肺细胞凋亡和磷酯酰肌醇-3激酶(PI3K)表达的影响。方法受孕SD大鼠分别于孕第15天孕囊注射脂多糖(LPS)或磷酸盐缓冲液(PBS);新生大鼠生后24 h内分组,给予60%高氧暴露;rhEPO干预组在高氧暴露第1天起,隔天皮下注射rhEPO(1 200 IU/kg)共7次;在高氧暴露的第1、7、14天处死新生大鼠;采用TUNEL法检测肺细胞凋亡,RT-PCR法检测PI3K mRNA表达。结果 LPS和生后高氧暴露均可引起新生大鼠肺细胞凋亡指数增高,肺组织PI3K mRNA表达降低,第7、14天时各组间的差异有统计学意义(P均<0.05);rhEPO干预可明显减少肺细胞凋亡,提高肺组织PI3K mRNA表达,第7、14天时相应各组的差异有统计学意义(P均<0.05)。结论宫内炎性暴露和高氧可引起新生大鼠肺细胞凋亡增多,rhEPO可明显减少肺细胞凋亡,其机制可能与肺组织PI3K mRNA表达有关。

Objectives To study the effect of recombinant human erythropoietin （rhEPO） on PI3K gene expression and apoptosis in the lungs of neonatal rats exposed to intraamniotic lipopolysaccharide （LPS） and hyperoxia. Methods LPS or PBS was injected to pregnant Sprague-Dawley rats on 15th day of gestation. After birth, the newborn rats were exposed to 60% oxygen in 24 hours. In rhEPO intervention group, rhEPO （12001U/kg） was administrated subcutaneously on the other day, total 7 times after first day of hyperoxia exposure. Lung cell apoptosis was evaluated by TUNEL assay and the levels of PI3K mRNA expression were detected using RT-PCR. Results The numbers of lung cell apoptosis increased and the levels of PI3K mRNA expression decreased due to intraamniotie injection of LPS and exposure of kyperoxia. Statistial significant were observed on 7th and 14th day of hyperoxia exposure. After rhEPO intervention, the numbers of lung cell apoptosis decreased and the levels of PI3K mRNA expression increased. Conclusions LPS injected intraamniotic and hyperoxia exposure can increase the number of the lung cells with apoptosis, while rhEPO can reduce apoptosis obviously. The anti-apoptic mechanism of rhEPO may be related with PI3K mRNA expression.