麻黄碱对缺氧缺血新生大鼠海马神经细胞的保护作用

Ephedrine protects hippocampal neurons in neonatal rats after hypoxic-ischemic brain injury

目的观察麻黄碱(ephedrine,EPH)对大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)海马神经细胞凋亡及远期学习记忆能力的影响。方法新生SD大鼠(7日龄)按随机数字表法分为麻黄碱组(EPH组)、对照组(Con组)和假手术组(Sham组)。分别于HIBD后6、12h,1、3、7d采用免疫组织化学检测各组大鼠bcl-2蛋白和bax蛋白在海马区的表达,HIBD后4周Morris水迷宫测试其学习记忆能力。结果EPH组bcl-2表达较Con组显著增高,1d时达到高峰,3d后逐渐下降;bax蛋白表达较Con组明显降低,1d时最低;各组平均潜伏时间均逐渐缩短,EPH组3～5d时平均潜伏时间较Con组明显缩短。EPH组穿越平台次数及在目标象限游泳距离与总距离百分比均高于Con组。结论麻黄碱可使新生大鼠HIBD后海马bcl-2蛋白表达增加和bax蛋白表达减少,并能提高远期学习记忆能力。

Objective To explore the effects of ephedrine on the hippoeampal cell apoptosis and behavioral performance after hypoxia-isehemia brain injury in neonatal rats. Methods Totally 90 7-day rats were randomly divided into 3 groups, ephedrine treatment group, model group, and sham group. Hypoxia-ischemia brain injury model was established by permanently ligating right common carotid artery. Ephedrine （ 1.5 mg/kg, once per day） was injected intraperitoneally to the rats of ephedrine treatment group for 7 d, and the rats of mode/group was given normal saline at the same volume. At the following time interval of 6 and 12 h, and 1, 3, and 7 d after hypoxia, the expression of bel-2 and bax were detected in the hippocampal region by immuno- histoehemical staining. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze. Results Compared with model group, the expression of bcl-2 in the ephedrine treatment group was significantly increased after hypoxic-ischemic injury, peaked at 1 d and decreased in 3 d after operation. And the expression of bax in the ephedrine treatment group was decreased in 1 d after hypoxie-ischemia. The average time of escape latency was gradually decreased in each group. However, from the 3rd to 5th day, it was much shorter in ephedrine treatment group than in model group. In addition, the frequency platform passing in the ephedrine treatment group and the percentage of swimming distance traveled in the previous target quadrant was significantly greater than those of the control group. Conclusion Ephedrine upregulates bcl-2 and down-regulates bax in the hippoeampus of neonatal rats after hypoxia-ischemia, and improves their ability of learning and memory.