不同时间给予促红细胞生成素治疗对成年颅脑创伤大鼠认知功能及其神经可塑性的影响

Effect of Erythropoietin Therapy at Different Time on Cognitive Function and Neural Plasticity in Adult Traumatic Brain Injury Rats

摘要: 目的：比较成年脑外伤大鼠造模后，在不同时间给予EPO治疗，对大鼠认知功能和神经可塑性的影响。方法：选取3个月龄的健康雄性成年SD大鼠，利用CCI方法制作双侧前额叶重度损伤模型，分为干预组及对照组。干预组又分为3个亚组，分别在造模后1周、2周、3周进行EPO腹腔内注射治疗。造模4周后进行Morris水迷宫测试，最后取海马组织病理进行免疫组化染色，检测GAP-43、SYN含量。结果：1周或2周开始治疗组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周开始治疗组的认知功能改善和对照组相比均未达到显著性水平。在相同的治疗剂量(5000 U/kg)和疗程(连续3天)下，三个治疗组海马的GAP-43和SYN表达水平均较对照组有显著性差异(P < 0.05)，尤其是2周开始治疗组的GAP-43和SYN表达水平最高。结论：不管治疗开始的时间早或晚(伤后1至3周)，EPO治疗对神经可塑性都具有一定的促进作用，但是EPO的开始治疗时间对于改善脑外伤后认知功能障碍的疗效存在一定的影响，造模后1周至2周开始的疗效可能更好。

Abstract: Objective: To compare the effects of EPO therapy on cognitive function and neural plasticity in rats at different time after adult traumatic brain injury was modeled. Methods: 3-months-old healthy male adult SD rats were selected to make bilateral frontal lobe severe injury model by CCI method, which was divided into intervention group and control group. The intervention group was divided into 3 sub-groups, which were treated with EPO intraperitoneal injection at 1 weeks, 2 weeks and 3 weeks after the model was made. After 4 weeks of modeling, Morris water maze test and immunohistochemical staining were performed in the hippocampus to detect GAP-43 and SYN content. Results: The improvement of spatial learning and memory ability was the more obvious in the treatment group at 1 or 2 weeks. The improvement of cognitive function in the treatment group at 3 weeks did not reach a significant level compared with the control group. In the same treatment dosage (5000 U/kg) and time (3 consecutive days), the GAP-43 and SYN expression in the hippocampus of three treatment groups were significantly different from those in the control group, and especially the GAP-43 and SYN expression levels were the highest in the treatment group at the beginning of 2 weeks. Conclusion: No matter how early or late the treatment begins (1 - 3 weeks after the injury), EPO therapy has a certain effect on neural plasticity, but the initial treatment time of EPO has some effects on the improvement of cognitive function after traumatic brain injury, and the effect of 1 to 2 week groups may be better.