氨甲酰化促红细胞生成素衍生物对小鼠低氧脑损伤保护作用的研究

目的：观察氦甲酰化促红细胞生成素衍生物（CEPO）对低氧所致小鼠海马损伤的保护作用。方法：成年雄性C57／B6小鼠置低氧（8％O2）分别处理0,5、1．5、3和6h，记录各组小鼠复氧后连续6及30d的Y迷宫训练错误反应次数。用免疫组化检测海马神经元核蛋白（NeuN）。在此基础上，将经Y迷宫训练筛选的小鼠低氧处理6h，并分为3组：CEPO组、促红细胞生成素（EPO）组和生理盐水组，隔日1次分别腹腔注射CEPO、EPO和生理盐水，共15次。第10和30天对小鼠进行Y迷宫测试，记录错误反应次数。用NeuN免疫组化检测给予药物干预2次（72h）后各组小鼠海马神经元的脱失状况。结果：①低氧处理的小鼠学习能力明显下降，以低氧3h组和6h组尤为明显；第30天Y迷宫测试时，低氧6h组的错误反应次数最高；NeuN免疫染色显示低氧后复氧3d的各组小鼠海马各亚区神经元均有明显脱失，以低氧6h组最为明显。②第10和30天Y迷宫测试显示，低氧小鼠经CEPO或EPO干预后Y迷宫的错误反应次数明显低于生理盐水处理的小鼠；NeuN免疫染色显示低氧小鼠给予CEPO或EPO处理后海马神经元脱失明显少于生理盐水处理的小鼠。结论：低氧处理6h的小鼠学习和记忆能力明显降低，海马神经元损伤严重。CEPO具有与EPO相似的减轻低氧所致学习和记忆损伤、减少海马神经元脱失的作用。

Protective Role of Carbamylated Erythropoietin in Hypoxic Mice Brain

Aim： To elucidate the effect of hypoxia on learning and memory as well as the loss of hippocampus neurons and study whether carbamylated erythropoietin remains the capability of neuroprotective in hypoxia-induced cerebral injury in mice. Methods： Mice were exposed to hypoxia （8% O2） for 0.5 h, 1.5 h, 3 h and 6 h, respectively. The error number of mice in Y maze test was recorded in 6 consequent days just after hypoxia and the day of 30th. The expression of NeuN in hippocampus was detected by immuno-histochemistry. The mice which has passed the Y maze tests were first treated with hypoxia for 6 h, and then they were administered EPO, CEPO and saline by i.p. every the other day in 30 consequent days, respectively. The error number and total react time of Y maze test were recorded at the 10th and the 30th day. The loss of hippocampus neurons was observed by NeuN immuno-histochemistry. Results： （1） Y maze test demonstrated a timedependent learning ability deficit after hypoxia, especially in hypoxia 3 h and 6 h groups. When tested 30 days after reoxygen, Y maze test showed that the mice in hypoxia 6 h group had a significant higher error number in 10 tests. At 3 days after reoxygen, the number of NeuN positive neurons in CA1 was significantly decreased in all regions of the hippocampus, especially in hypoxia 6 h group. （2） Y maze test showed that the error number was distinctly decreased in hypoxic mice which were received CEPO or EPO at 10d and 30d after hypoxia, compared with the mice administered saline. The NeuN immuno-histochemistry showed that the neuron loss in hippocampus in both EPO and CEPO groups was significantly less than that in saline group. Conclusion： The hypoxia （8%O2） treatment for 6 h could cause the deficit of learning and memory ability and neuron loss of hippocampus in mice. CEPO, like EPO, had a role in the improvement of learning and memory ability, and reduced the neuron loss in mouse brain following hypoxia.