促红细胞生成素治疗不同月龄大鼠脑外伤后认知障碍的疗效及其神经可塑性的研究

Research on Effect of Erythropoietin Therapy on Cognitive Impairment and Neural Plasticity after Traumatic Brain Injury in Rats with Different Month-Age

摘要: 目的：比较促红细胞生成素治疗不同月龄脑外伤模型大鼠认知功能的疗效差异，探索其对神经可塑性的影响。方法：分别选取1、2、3个月龄的健康雄性SD大鼠，利用CCI方法制作重度脑外伤模型，分为干预组及对照组。干预组分别在造模后1周进行Epo腹腔内注射治疗，对照组注射等量的生理盐水。造模4周后进行Morris水迷宫测试，最后处死动物，进行海马组织免疫组化染色，检测GAP-43、Syn含量。结果：1月龄大鼠的空间学习和记忆能力改善最为明显，和对照组相比均达到了显著性水平；而3月龄大鼠的认知功能改善均未达到显著性水平。在相同的治疗时间和剂量情况下，三个月龄组海马的GAP-43和Syn表达水平治疗后均较对照组有显著性差异，尤其是1月龄组治疗后Syn表达水平最高。结论：不管成年或未成年脑外伤大鼠，Epo治疗对神经重塑都具有一定的促进作用，但成年大鼠这种作用对认知功能的改善效果不及未成年大鼠那么明显，或者是可能需要更长疗程才能体现。

Abstract: Objective: To compare the effect difference of erythropoietin therapy on cognitive function in trau-matic brain injury rats with different month-age, and to explore its effect on neural plasticity. Methods: 1, 2, 3 month-age healthy male SD rats were selected, and the CCI method was used to make the severe traumatic brain injury model, which was divided into intervention group and con-trol group. The intervention group was treated with Epo intraperitoneal injection after 1 week, and the control group was injected with equal saline. After 4 weeks of modeling, Morris Water Maze test was taken for each rat, then the hippocampal immunohistochemical staining were done for detec-tion of GAP-43 and Syn after final execution of all rats. Results: The improvement of spatial learning and memory ability of 1 month-age rats was the most obvious, compared with the control group, it reached a significant level. However, the improvement of cognitive function of 3 month-age rats did not reach a significant level. In the same treatment time and dosage, the level of GAP-43 and Syn expression in hippocampus of 3 month-age group was significantly different from the control group, especially the level of Syn expression in the 1 month-age group after treatment. Conclusion: Re-gardless of adult or underage rats with traumatic brain injury, Epo therapy has a certain promoting effect on neural plasticity, but the effect of adult rats on cognitive function is less obvious than that of underage rats, or it may take longer period of time to manifest.