摘要
[目的]探讨促红细胞生成素(EPO)对高氧脑损伤新生大鼠CCAAT增强子结合蛋白同源蛋白(CHOP)及葡萄糖调节蛋白78(GRP78)表达的影响.[方法]取足月新生Wistar大鼠随机分为正常对照组(FiO_2为21%)、高氧组(FiO_2高于85%)和高氧+EPO组(FiO_2高于85%).将正常对照组新生大鼠置于室内空气中饲养,高氧组和高氧+EPO组大鼠置于FiO_2高于85%的室内玻璃箱中饲养.实验第1 d起,高氧+EPO组大鼠每日腹腔注射给予EPO(800 U/kg),实验第1,3,7,14 d时测定各组大鼠脑组织湿/干质量(W/D)比值,采用蛋白免疫印记法检测脑组织中CHOP,GRP78蛋白表达水平.[结果]高氧组新生大鼠第1,3,7,14 d时的脑组织W/D值较正常对照组显著升高(P<0.05),高氧下暴露时间越长,W/D值升高越显著;高氧+EPO组新生大鼠脑组织含水量较高氧组显著降低(P<0.05).高氧组第1,3,7,14 d时的CHOP和GRP78蛋白表达水平较正常对照组显著升高(P<0.05),高氧+EPO组CHOP,GRP78蛋白表达水平较高氧组显著降低(P<0.05).[结论] EPO可缓解高氧引起的新生大鼠脑水肿,对高氧脑损伤具有神经保护作用,其机制认为可能与下调CHOP和GRP78蛋白表达有关系.
OBJECTIVE To investigate the effects of erythropoietin(EPO) on the expressions CCAAT enhancer binding protein homologous protein(CHOP) and glucose regulated protein 78(GRP78) in neonatal rats with hyperoxic brain injury. METHODS Full-term newborn Wistar rats were randomly divided into control group(FiO_2=21%), hyperoxia group(FiO_2>85%) and hyperoxia + EPO group(FiO_2>85%). The newborn rats in the control group were placed in indoor air, and the rats in the hyperoxia and the hyperoxia+EPO group were placed in an indoor glass box with FiO_2 more than 85%. From the first day of the experiment, the rats in the hyperoxia + EPO group were intraperitoneally injected with EPO(800 U/kg), and the wet/dry mass(W/D) ratio of brain tissue was measured at day 1, 3, 7 and 14. Protein immunoblotting was used to detect the expression levels of CHOP and GRP78 protein in brain tissue. RESULTS The W/D values of brain tissue on the 1st, 3rd, 7th and 14th day of neonatal rats in the hyperoxia group were higher than those in the control group(P<0.05). The longer the exposure time under high oxygen, the more obvious the increase of W/D values. The water content of neonatal rat brain tissue in the hyperoxia + EPO group was obviously lower than that in the hyperoxia group(P<0.05). The expressions of CHOP and GRP78 protein in the hyperoxia group were significantly higher than those in the control group at day 1, 3, 7 and 14(P<0.05). The expression of CHOP and GRP78 protein in the hyperoxia + EPO group was significantly lower than those in the hyperoxia group(P<0.05). CONCLUSION EPO could alleviate cerebral edema induced by hyperoxia in neonatal rats and had neuroprotective effects on hyperoxic brain injury, which might be related to the down-regulation of CHOP and GRP78 protein expression.
引文
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