促红细胞生成素对新生鼠缺氧缺血性脑损伤后学习记忆功能的影响

目的动态观察促红细胞生长素（erythropoietin,EPO）早期对新生大鼠缺氧缺血性脑损伤后（hypoxic ischemicbrain damage,HIBD）学习记忆功能的影响,从神经行为学方面探索不同剂量EPO早期对新生鼠HIBD的保护作用,为临床早期应用EPO治疗新生儿缺氧缺血性脑病选择合适的治疗剂量提供实验参考。方法新生7日龄Wistar大鼠40只随机分为HIBD生理盐水对照组、假手术组、EPO治疗Ⅰ组、EPO治疗Ⅱ组、EPO治疗Ⅲ组,每组8只,通过结扎并剪断7日龄新生大鼠右侧颈总动脉,吸入8%O2＋92%N2的低氧气源2小时制备新生鼠HIBD模型。EPO治疗Ⅰ、Ⅱ、Ⅲ组分别于缺氧缺血完成后即刻注射rhEPO5u/g、10u/g、15u/g,HIBD对照组即刻注射生理盐水0.5mL/只,连续14天,通过Morris水迷宫实验观察五组大鼠的学习记忆功能。结果①学习能力：五组大鼠逃逸伏期总体比较差异有统计学意义（〈0.05）,其中假手术组最短,EPO治疗Ⅰ、Ⅱ、Ⅲ组次之,HIBD对照组最长。②记忆能力：HIBD对照组穿环指数与假手术组、EPO治疗Ⅰ、Ⅱ、Ⅲ组间差异均有统计学意义（〈0.05）,而假手术组与EPO治疗Ⅰ、Ⅱ、Ⅲ组间比较,差异无统计学意义（〉0.05）,EPO治疗Ⅰ、Ⅱ、Ⅲ组间相互比较,差异亦无统计学意义（〉0.05）。结论①EPO早期治疗可改善新生大鼠缺氧缺血性脑损伤后的学习和记忆功能;②通过对本试验的选择的三种EPO实验剂量对新生大鼠HIBD的影响结果表明,随着EPO剂量的增加并不能增强脑保护作用。

Effects of erythropoietin on the learning ability and memory capacity in neonatal rat brain after hypoxic-ischemic brain damage

Objective To investigate the effects of erythropoietin（EPO）on the learning ability and memory capacity by using the Morris water maze,in order to obtain the experimental evidences of the suitable therapeutic dose of the EPO for hypoxic-ischemic encephalopathy of neonates.Methods Forty neonatal Wistar rats were divided into five groups randomly：the group of the HIBD,the control group of normal sodium and the trial group of EPOⅠ、Ⅱ、Ⅲ,each group were eight,the HIBD models of neonatal Wistar rats were made by shearing right arteria carotis communis and then breathing 8%O2＋92%N2 for two hours.the trial groups of EPOⅠ、Ⅱ、Ⅲ were injected intraperitonally separate rhEPO 5u/g、10u/g、15u/g for fourteen days since operation,the control group of the HIBD was injected intraperitonally 0.5mL NS as a pair,the other rats were taken into the sham operation group.Each of five group＇s spatial cognitive capability was evaluated by using the Morris water maze.Results ① Learning ability： The latency to escape was significantly difference in five groups（P0.05）,the sham group is the shorter compared with the EPOⅠ、Ⅱ、Ⅲ treated groups,the control group of HIBD is the longest.②Memory capacity： The frequency of passing the platform was a significantly difference in five groups;there is a significantly difference in the sham operation group and the EPOⅠ、Ⅱ、Ⅲ treated group compared with the control group of HIBD（P0.05）,but there was no significant difference between the sham operation group and the EPOⅠ、Ⅱ、Ⅲ treated group（P0.05）.and also no significant difference in the EPOⅠ、the EPOⅡand the EPOⅢ groups too（P0.05）.Conclusions ① EPO early intervention can improve the ability of learning and memory in the neonatal rats with HIBD;② The result show it could not improve the neuroprotective effects by increasing dose of EPO.