摘要：

目的 探讨红细胞生成素对海人酸致模型大鼠癫痫发作及空间学习和记忆能力的影响。方法 共96 只Sprague-Dawley 大鼠随机分为4 组，观察不同处理组大鼠行为学变化，Morris 水迷宫实验定位航行实验和空间探索实验评价大鼠空间学习和记忆能力，Western blotting 法检测大鼠海马组织p38 有丝分裂原激活蛋白激酶（p38MAPK）、c-Myc 和caspase-3 表达变化。结果 红细胞生成素组大鼠癫痫发作程度减轻（P = 0.000）。与模型组相比，红细胞生成素低、高剂量组大鼠逃避潜伏期缩短（P = 0.043，0.000），第1 象限停留时间延长（P = 0.000，0.000），穿越平台次数增加（P = 0.000，0.046），并以高剂量组显著（均P = 0.000）；而且，大鼠海马组织p38MAPK（P = 0.000，0.000）、c-Myc（P = 0.009，0.000）和caspase-3（P = 0.003，0.000）表达水平降低，并以高剂量组明显（P = 0.040，0.030，0.048）。结论 红细胞生成素可以减轻大鼠癫痫发作程度，提高大鼠空间学习和记忆能力，其作用机制可能与红细胞生成素抑制p38MAPK 及其下游c-Myc和caspase-3表达，最终减少神经元凋亡有关。

关键词: 红细胞生成素, 癫痫, 红藻氨酸, 认知障碍, 海马, 疾病模型, 动物

Abstract:

Objective  To observe the effects of erythropoietin (EPO) on the behaviors and abilities of spatial learning and memory of kainic acid (KA)-induced epileptic rats. Methods  A total of 96 rats were randomly divided into 4 groups: control group, model group, low-dose EPO pretreated group and high-dose EPO pretreated group. After treatment with relevant reagents, the behaviors of rats in each group were observed. The abilities of spatial learning and memory were evaluated by Morris water maze test. Expressions of apoptosis-related factors: p38MAPK, c-Myc and caspase-3 were detected by Western blotting.  Results  Behavior observation showed seizures in EPO groups reduced (P = 0.000). Compared with model group, rats in EPO groups had significantly reduced escape latency in positioning navigation trial (P = 0.043, 0.000), significantly prolonged first quadrant latency (P = 0.000, 0.000) and increased platform crossing index in spatial probe trial (P = 0.000, 0.046), expressly in high-dose EPO group (P = 0.000, for all). Expressions of p38MAPK (P = 0.000, 0.000), c-Myc (P = 0.009, 0.000) and caspase-3 (P = 0.003, 0.000) in rat hippocampus were significantly decreased in EPO groups than that in model group, expressly in high-dose EPO group (P = 0.040, 0.030, 0.048).  Conclusions Erythropoietin can reduce the attack of epileptic rats and increase the ability of spatial learning and memory in KA-induced epileptic rats. The mechanism may be associated with depressing the expression of p38MAPK and downstream c-Myc and caspase-3, finally reducing neuronal apoptosis.

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