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目的探讨新生鼠缺氧缺血后海马缺氧诱导因子1α(HIF-1α)和脑源性促红细胞生成素(EPO)的表达。方法对7日龄SD新生大鼠结扎左侧颈总动脉并暴露在低氧环境建立新生大鼠缺氧缺血性脑损伤(HIBD)模型,以及单纯持续暴露在低氧环境建立低氧诱导模型。新生大鼠HIBD后0、1、6、16h和1、3、7天,用免疫组织化学染色观察海马HIF-1α和EPO的表达情况。低氧诱导0.5、1、2、3、5h后免疫组织化学染色法观察海马HIF-1α的表达。结果 HIBD组随复氧时间的延长,海马CA1区EPO阳性细胞计数先增加后降低,16h最高,差异有统计学意义(P<0.001),对照组各时间点差异无统计学意义(P>0.05);HIBD组各时间点EPO阳性细胞数均高于对照组(P<0.001)。HIBD组缺氧缺血后即刻(0h)海马齿状回见少量HIF-1α阳性细胞,复氧后各时间点和对照组均未见HIF-1α阳性细胞;持续暴露在低氧环境0.5h,HIF-1α开始表达,至3h时HIF-1α表达达高峰。常氧对照组未见HIF-1α表达。结论新生大鼠HIBD后内源性EPO分泌增加,低氧可诱导HIF-1α表达,推测HIF-1α/EPO缺氧信号转导系统可能参与缺氧缺血后海马神经元形成。
Objective To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and brain-derived erythropoietin (EPO) in hippocampus of neonatal rats after hypoxia-ischemia. Methods Hypoxic-ischemic brain damage (HIBD) models were established in neonatal SD rats exposed to hypoxia at 7-day-old SD neonatal rats, and hypoxia-induced model . The expression of HIF-1α and EPO in the hippocampus were observed by immunohistochemical staining at 0,1,6,16 and 1,3,7 days after HIBD in neonatal rats. The expression of HIF-1α in the hippocampus was observed by immunohistochemical staining at 0.5, 1, 2, 3, 5 h after hypoxia. Results With the prolongation of reoxygenation time, the number of EPO positive cells in hippocampal CA1 area first increased and then decreased, with the highest level at 16h (P <0.001). There was no significant difference in the control group at each time point (P> 0.05 ). The number of EPO positive cells in HIBD group at each time point was higher than that in control group (P <0.001). A small amount of HIF-1α positive cells were seen in hippocampal dentate gyrus of HIBD group immediately after hypoxia-ischemia (0h). HIF-1α positive cells were not seen at all time points after reoxygenation and in control group. After continuous exposure to hypoxia for 0.5h, HIF-1α began to express, up to 3h HIF-1α expression peak. Oxygen control group no HIF-1α expression. Conclusions The endogenous EPO secretion increased after HIBD in neonatal rats and hypoxia induced the expression of HIF-1α. It is speculated that HIF-1α / EPO hypoxia signal transduction system may be involved in the formation of hippocampal neurons after hypoxic-ischemia.