Orexin-1受体拮抗剂对慢性点燃癫大鼠学习记忆的影响及海马神经细胞的增殖变化  

Effect of Orexin-1 Receptor Antagonist on the Ability of Learning and Memory and Neuronal Cell Proliferation of the Hippocampus in Chronic Pentylenetetrazol-kindled Rats

作　　者：赵璇[1] 唐吉友[1] 任延艳[1] 刘小民[1] 杨位霞[1] 朱梅佳[1] 王爱华[1] 

机构地区：[1]山东大学附属千佛山医院神经内科,250014

出　　处：《中国临床神经科学》2012年第3期247-253,共7页Chinese Journal of Clinical Neurosciences

基　　金：教育部留学回国人员科研启动基金(编号:20101108);山东省自然科学基金资助项目(编号:Y2008C1610);山东省科技攻关计划资助项目(编号:2010GSF10244)

摘　　要：目的:研究orexin-1受体(OX1R)拮抗剂(SB334867,SB)对戊四氮(PTZ)慢性点燃癫大鼠空间学习记忆能力及海马齿状回神经细胞增殖的影响。方法:Wistar大鼠随机分为①对照组[腹腔和侧脑室均注射生理盐水(NS)];②PTZ组(腹腔注射PTZ+侧脑室注射NS);③PTZ+orexin-A(OXA)组(腹腔注射PTZ+侧脑室注射OXA);④PTZ+SB组(腹腔注射PTZ+侧脑室注射SB);⑤PTZ+SB+OXA组(腹腔注射PTZ+侧脑室注射SB和OXA)。观察各组大鼠的空间学习记忆能力及海马齿状回区BrdU+和BrdU+/NeuN+细胞的表达。结果:与PTZ+OXA组比较,PTZ+SB+OXA组大鼠逃避潜伏期延长、穿越平台象限的次数减少(P<0.05)。免疫荧光显示,PTZ+OXA组大鼠齿状回区BrdU+和BrdU+/NeuN+细胞表达增多(P<0.01),而PTZ+SB+OXA组大鼠齿状回区BrdU+/NeuN+细胞表达比PTZ+OXA组减少(P<0.01)。结论:OXA通过OX1R能改善癫大鼠的空间学习记忆能力,可能与OX1R介导的海马齿状回神经细胞增殖与分化作用有关。Aim： To investigate the effects of orexin-1 receptor（OX1R） antagonist on spatial learning and memory as well as neuronal cell proliferation of the hippocampus in the pentylenetetrazol（PTZ）-kindled rats.Methods： Sixty adult male Wistar rats were randomly divided into five groups： non-kindled（NS＋NS）,PTZ＋saline（PTZ＋NS）,PTZ＋orexin-A（PTZ＋OXA）,PTZ＋OX1R antagonist SB334867（PTZ＋SB） and PTZ＋SB＋OXA groups.Morris water maze and immunofluorescence techniques were used to investigate the spatial learning and memory and expressions of bromodeoxyuridine（BrdU） and BrdU/NeuN in the hippocampal dentate gyrus.Results： Compared with the PTZ＋OXA group,the latency of escape platform was significantly increased with a remarkable reduction in number of crossing the platform in 120 s in the PTZ＋SB＋OXA group（P0.05）.By using the immunofluorescence of BrdU and NeuN,it has been demonstrated that the BrdU and BrdU/NeuN positive cells in the hippocampal dentate gyrus were significantly increased in the PTZ＋OXA rats when compared with the PTZ＋NS rats.However,this effect of orexin-A was inhibited by the OX1R antagonist SB334867.Conclusion： The learning and memory ability of chronic PTZ-kindled rats can be improved by orexin-A via OX1R.This could be due to the OX1R-mediated cell proliferation in hippocampal dentate gyrus and the regulation of the integration of newborn neurons into neuronal circuits to receive the input of normal signal.

关 键 词：癫 学习记忆 Orexin-1受体 神经再生 

分 类 号：R742.1[医药卫生—神经病学与精神病学]