摘要
目的探讨促红细胞生成素(EPO)对阿尔茨海默病(AD)样大鼠记忆能力和凋亡相关蛋白的影响。方法雄性Wistar大鼠应用Y迷宫进行空间定向学习和记忆训练5 d后,将达到学会标准的48只大鼠随机分为4组:正常对照组、生理盐水(NS)组、模型组和EPO治疗组,每组12只。其中NS组大鼠双侧海马注射NS各5μL,模型组和EPO治疗组大鼠双侧海马注射凝聚态β-淀粉样蛋白(Aβ)各5μL造模。EPO治疗组大鼠从造模手术当天按5 000 IU·kg-1腹腔注射EPO,隔日1次。术后第10天Y迷宫法检测各组大鼠空间定向学习和记忆能力,透射电镜观察海马线粒体和突触结构的改变,采用免疫组织化学技术检测各组大鼠海马组织Bcl-2、Bax蛋白的表达。结果与NS组比较,模型组大鼠学习记忆能力显著下降(P<0.05);与模型组比较,EPO治疗组大鼠Y迷宫作业尝试次数减少,错误反应次数减少,全天总反应时间缩短,差异有统计学意义(P<0.05)。透射电镜结果显示,正常对照组和NS组大鼠神经细胞结构完整,线粒体膜、嵴完整,神经轴突和神经突触结构完整;EPO治疗组大鼠海马线粒体和神经突触基本正常;模型组大鼠海马线粒体结构破坏,线粒体肿胀,线粒体嵴断裂,结构紊乱,神经突触密度降低,突触膜增厚,突触间隙不清,突触小泡数量减少。与NS组比较,模型组大鼠海马Bcl-2蛋白表达减弱,Bax蛋白表达增强;与模型组比较,EPO治疗组大鼠海马Bcl-2蛋白表达增强,Bax蛋白表达减弱,差异均有统计学意义(P<0.05)。结论EPO可以显著改善AD样大鼠的空间记忆能力,减轻Aβ对大鼠海马超微结构的破坏。EPO可能通过调节Bcl-2/Bax水平抑制神经元的凋亡,这可能是EPO改善AD大鼠认知功能障碍的机制之一。
Objective To investigate the effect of erythropoietin（ EPO） on Alzheimer rat＇s memory ability and expression of apoptosis-related proteins. Methods Space orientation and memory of Wistar male rats were trained by using Y maze for 5 days. Forty-eight rats complied with learned standard were randomly divided into four groups（ n = 12） ： normal control group,normal sodium（ NS） group,model group and EPO treated group. Normal sodium 5 μL was injected into bilateral hippocampuses of normal sodium group. Condensed Aβ 5 μL was injected into bilateral hippocampuses of model group and EPO treated group. EPO treated group was injected with 5 000 IU·kg- 1EPO once every other day since the day of model operation. On the 10thday after operation,space orientation and memory of Wistar male rats were assayed by Y maze. The changes of mitochondria and synaptic structure of hippocampus were observed by transmission electron microscope. Expressions of Bcl-2and Bax in rats＇ hippocampus were assayed by immunohistochemistry. Results Compared with the NS group,the ability of study and memory of rats in model group was obviously declined（ P〈0. 05）. Compared with the model group,the attempt and error number of Y maze tasks of rats in EPO treated group reduced and the total reactive time per day significantly shortened.There were significant differences between them（ P〈0. 05）. The transmission electron microscope showed that normal control group and NS group had integral structure,mitochondrial membrane and ridge of neurocyte,normal nerve axons and nerve synapses. In EPO group,the mitochondria and nerve synapses of hippocampus were basically normal. However,in model group the mitochondria of rats＇ hippocampus was demolished and became swelling,the mitochondrial ridge disappeared and its structure became disordered,the density of nerve synapses reduced,the synaptolemma was thick,meanwhile the synaptic cleft became unclear,and the number of synaptic vesicle decreased. Compared with NS group,Bcl-2 of rats＇ hippocampus decreased,but Bax increased in model group. Compared with model group,Bcl-2 of rats＇ hippocampus increased,but Bax decreased in EPO treated group（ P〈0. 05）. Conclusions EPO can reduce the damage of AD rats＇ memory ability and lighten the destruction of hippocampus ultrastructure caused by Aβ. EPO may inhibit apoptosis of neuron by regulating level of Bcl-2 /Bax. It may be one of the mechanisms to improve the cognitive dysfunction of AD rats by EPO.
出处
《新乡医学院学报》
CAS
2014年第8期599-602,共4页
Journal of Xinxiang Medical University
基金
河南省医学科技攻关计划项目(编号:200903117)
作者简介
李宜培（1981-），女，河南社旗人，硕士，讲师，研究方向：阿尔茨海默病的病理生理学。
通信作者：王黎（1962-），男，河南郑州人，博士，教授，硕士研究生导师，研究方向：老年痴呆的病理生理学。
