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目的:观察氨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%O_2)分别处理0.5、1.5、3和6h,记录各组小鼠复氧后连续6及30 d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(72 h)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3 h组和6 h组尤为明显;第30天Y迷宫测试时,低氧6 h组的错误反应次数最高;NeuN免疫染色显示低氧后复氧3 d的各组小鼠海马各亚区神经元均有明显脱失,以低氧6 h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。
Objective: To observe the protective effect of carbamylated erythropoietin derivative (CEPO) on hypoxia-induced hippocampal lesion in mice. Methods: Adult male C57 / B6 mice were treated with hypoxia (8% O 2) for 0.5, 1.5, 3 and 6 hours respectively. The number of Y maze training errors after 6 and 30 days of reoxygenation was recorded. Immunohistochemistry was used to detect the nuclear protein (NeuN) of hippocampal neurons. On this basis, the mice screened by Y maze training were treated with hypoxia for 6 hours and divided into 3 groups: CEPO group, EPO group and saline group. CEPO and EPO And saline, a total of 15 times. Mice were subjected to a Y-maze test on days 10 and 30 to record the number of false reactions. NeuN immunohistochemistry was used to detect the loss of hippocampal neurons in each group after twice intervention (72 h). Results: ① The learning ability of hypoxia-treated mice decreased significantly, especially in hypoxia 3 h group and 6 h group; the number of false reaction in hypoxia 6 h group was the highest at Y-maze test on day 30; NeuN immunostaining After 3 days of hypoxia, the hippocampal neurons in each subgroup of hippocampus were obviously lost, especially in hypoxia 6 h group. ② On the 10th and 30th days, the Y-maze test showed that the number of Y-mazes was significantly lower than that of the saline-treated mice after hypoxic exposure to CEPO or EPO. NeuN immunostaining showed that hypoxic mice were given CEPO or EPO Hippocampal neurons lost significantly less than saline-treated mice. CONCLUSION: The learning and memory abilities of mice treated with hypoxia for 6h are significantly reduced, and the damage of hippocampal neurons is serious. CEPO is similar to EPO in reducing hypoxia-induced learning and memory impairment and reducing the loss of hippocampal neurons.