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

Effect of topiramate on ability of learning and memory and expression of hippocampal GAP-43mRNA in developmental status epilepticus rats

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(GAP-43)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RT-PCR方法检测大鼠海马组织GAP-43 mRNA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(P<0.05),海马组织GAP-43 mRNA相对吸光度值降低(P<0.05)。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GAP4-3 mRNA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(P<0.05),海马组织GAP-43 mRNA相对吸光度值降低(P<0.05)。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GAP-43表达有关。

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 80 mg·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-43 mRNA in hippoeampus was detected by reverse transcription polymerase chain reaction. Results Compared with the normal group, learning and memory dysfunction were observed in epileptic rats（ P 〈 0.05 ） , relative absorbance of GAP-43 mRNA decreased significantly （P 〈 0.05 ）. Compared with the model group, TPM small- and middle-dose groups showed no different in learning and memory function and relative absorbance of GAP-43 mRNA, but TPM large-dose appeared to impair the learning and memory function （ P 〈 0.05 ） and relative absorbance of GAP-43 mRNA decreased significantly（ P 〈 0.05）. Conclusion SE can damages ability of learning and memory in immature rats. Large-dose TPM appears to aggravate the learning and memory function of epileptic rats ,which might be relevant to its regulating effect on the expression of GAP-43 in hippocampus.