雷帕霉素对匹罗卡品诱导的癫痫小鼠学习记忆的改善作用  

Rapamycin improves learning and memory ability in ICR mice with pilocarpine-induced temporal lobe epilepsy

作　　者：张华丹[1] 谢雅聪 翁灵 张宇辰[1] 史琼瑶[1] 陈涛[1] 曾玲晖[1] 

机构地区：[1]浙江大学城市学院医学院,浙江杭州310015

出　　处：《浙江大学学报（医学版）》2013年第6期602-608,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：教育部留学回国科研启动基金资助项目;杭州市科技发展计划资助项目(20100333T24);浙江省科技厅实验动物平台资助项目(2013C37026)

摘　　要：目的：探讨mTOR抑制剂雷帕霉素对匹罗卡品致痫ICR小鼠学习记忆的改善作用。方法：成年雄性ICR小鼠160只，随机分为溶剂对照组、雷帕霉素对照组、模型组、雷帕霉素前给药组和后给药组。其中模型组、前给药组和后给药组均经腹腔注射匹罗卡品（pilocarpine，PILO）诱导小鼠急性癫痫发作，雷帕霉素治疗组分别在致痫前后腹腔给药3d。学习记忆水平的检测采用水迷宫、Y迷宫及旷场等行为学方法。FJB染色用于神经元细胞凋亡的检测。Timm染色用于检测苔藓纤维发芽。结果：PILO致痫后ICR小鼠虽然并未出现明显神经元细胞死亡，但在PILO诱导癫痫后的7～10d出现明显的学习记忆损伤，与对照组相比表现为平台逃避潜伏期延长（P〈0．05）、正确反映次数减少（P〈0．01）和穿格次数下降（P〈0．05）；致痫前给予雷帕霉素治疗能显著逆转PILO所致的平台逃避潜伏期延长（P〈0．001）、正确反映次数减少（P〈0．01）和穿格次数下降（P〈0．01），后给药组亦能逆转PILO所致的平台逃避潜伏期延长（P〈0．05）和穿格次数下降（P〈0．01）。同时，雷帕霉素能明显抑制PILO致痫后苔藓纤维发芽（P〈0．001）。结论：雷帕霉素能改善PILO致痫后小鼠学习记忆障碍，其作用机理有待进一步探讨。Objective： To investigate the effect of rapamycin, an mTOR inhibitor, on learning and memory ability of mice with pilocarpine （PILO） -induced seizure. Methods： One hundred and sixty male adult ICR mice were randomly grouped as vehicle control （ n = 20 ）, rapamycin control （ n = 20 ）, PILO model （ n = 40）, rapamycin pre-treatment （ n = 40） and rapamycin post-treatment （ n = 40 ）. PILO model and rapamycin treatment groups were injected with PILO to induce temporal lobe seizure. Rapamycin was administrated for 3 days before or after seizure. Morris water maze, Y maze and open field were used for the assessment of learning and memory, and FJB and Timm staining were conducted to detect the neuronal cell death and mossy fiber sprouting, respectively. Results： No significant cell death was observed in the mice with PILO-induced seizure. The learning and memory were impaired in mice 7 to 10 days after PILO- induced seizure, which was evident by prolongation of avoiding latency （ P 〈 0.05 ）, decrease in number of correct reaction （ P 〈 0.01 ） and number of crossing （ P 〈 0.05 ）. Treatment with rapamycin both pre- and post- PILO injection reversed seizure-induced cognitive impairment. In addition, rapamycin inhibited the mossy fiber sprouting after seizure （ P 〈 0. 001 ）. Conclusion： Rapamycin improves learning and memory ability in ICR mice after PILO-induced seizure, and its mechanism needs to be further studied.

关 键 词：毛果芸香西茂 药理学 癫痫 药物疗法 西罗莫司 治疗应用 记忆 随机对照试验 雷帕霉素 学习记忆 匹罗卡品 

分 类 号：R742.1[医药卫生—神经病学与精神病学]