托吡酯对发育期癫痫大鼠学习记忆能力及海马组织GAP 43表达的影响.doc

托吡酯对发育期癫痫大鼠学习记忆能力及海马组织GAP 43表达的影响 【摘要】目的研究托吡酯(TPM)对戊四氮(PTZ)致癫痫的发育期大鼠学习记忆能力及海马组织神经生长相关蛋白（GAP43)表达的影响。方法从80只6周龄健康雄性SD大鼠中随机抽取16只作为正常对照组；余64只以PTZ腹腔注射,制作癫痫持续状态（SE）模型，再随机分为模型对照组、TPM低剂量组、TPM中剂量组和TPM高剂量组,每组16只。TPM低、中、高剂量组分别给予TPM 20、40和80 mg·kg- 1灌胃。2周后应用Morris水迷宫、Y迷宫评价大鼠的学习记忆能力，应用RTPCR 方法检测大鼠海马组织GAP43mRNA表达变化。结果发育期癫痫大鼠的学习记忆能力较正常大鼠明显下降（P0.05），海马组织GAP43mRNA相对吸光度值降低（P0.05）。癫痫大鼠学习记忆能力经低、中剂量TPM干预后未发生明显变化，海马组织GAP43mRNA相对吸光度值也无明显变化；经高剂量TPM干预后学习记忆能力则明显下降（P0.05），海马组织GAP43mRNA相对吸光度值降低（P0.05）。结论SE后发育期大鼠的学习记忆能力受损，大剂量应用TPM可加重这一损害，该损害可能与调节海马GAP43表达有关。 【关键词】 癫痫 戊四氮 海马 托吡酯 学习记忆 神经生长相关蛋白 Effect of topiramate on ability of learning and memory and expression of hippocampal GAP 43mRNA in developmental status epilepticus rats LI Yan,TANG Hong li,LUO Ping xiang(Department of Pediatrics,Zhongda Hospital,Southeast University,Nanjing 210009,China） Abstract:Objective To investigate the effect of topiramate on ability of learning and memory and the content of neuronalgrowth associated protein 43 （GAP 43） activity in hippocampus of pentetazole (PTZ) induced epileptic rats.Methods Sixteen of eighty immature healthy male SD rats were assigned normal control group randomly,sixty four were made developmental status epilepticus (SE)model by topiramate (TPM) and randomly divided into 4 equal groups:the model control group,TPM small dose group,TPM middle dose group,TPM large dose group.Dose of TPM 20,40 and 80mg.kg-1 were given respectively for two weeks.The ability of learning and memory was tested by Morris water maze and Y maze.The expression of GAP 43mRNA in hippocampus was detected by reverse transcription polymerase chain reaction.Results Compared with the normal group,learning and memory dysfunction were observed in epileptic rats(P0.05),relative absorbance of GAP 43mRNA decreased significantly(P0.05).Compared with the model group,TPM small and middle dose groups showed no different in learning and memory function and relative absorbance of GAP 43mRNA,but TPM large dose appeared to impair the learnin