小鼠匹鲁卡品诱导的癫痫持续状态模型改良研究

Improved Method for Status Epilepticus Induction in Mice with Pilocarpine

目的探讨小鼠匹鲁卡品癫痫持续状态模型(status epilepticus,SE)建立的优化给药策略。方法 98只ICR小鼠随机分为7组,每组14只,分别采用常规(一次量给药)或改良方法腹腔注射匹鲁卡品。改良方法为先给予150或200 mg·kg^(-1)匹鲁卡品,30 min内若未发作,则继续给予1~2次30~100 mg·kg^(-1)匹鲁卡品(给药时间间隔为30 min)。动物行为学结合海马脑电图用于评价SE成功诱导及动物猝死情况。结果常规方法:200 mg·kg^(-1)组(即一次量给予200 mg·kg^(-1)匹鲁卡品)造模成功4例,5例未SE发作,死亡5例;250 mg·kg^(-1)组造模成功3例,死亡11例;300 mg·kg^(-1)组动物全部死亡。改良方法:(150+50)mg·kg^(-1)改良组(先给予150 mg·kg^(-1)匹鲁卡品,若未发作则追加50 mg·kg^(-1)匹鲁卡品1~2次)造模成功6例,2例未SE发作,死亡6例;(150+100)mg·kg^(-1)改良组造模成功7例,死亡7例;(200+30)mg·kg^(-1)改良组造模成功6例,3例未SE发作,死亡5例;(200+50)mg·kg^(-1)改良组造模成功9例,死亡5例。结论常规一次量方法诱导小鼠SE模型时匹鲁卡品有效剂量较难控制,经改良后(200+50)mg·kg^(-1)的改良方法可能是小鼠匹鲁卡品SE模型建立的较优方法。

OBJECTIVE To explore the optimal strategies to establish pilocarpine model of status epilepticus （SE） in mice. METHODS The 98 ICR mice were randomly divided into seven groups, and SE model was established by intraperitoneal injection of pilocarpine with regular （single-dose of pilocarpine） or modified methods in each group. In modified methods, mice were administrated with 150 or 200 mg·kg^-1 pilocarpine, and then they were added 30-100 mg·kg^-1 pilocarpine every 30 min if SE were not induced. The SE state of mice were evaluated by the seizure behaviors and electroencephalography. RESULTS For regular methods： 4 mice were induced SE, 5 were no-SE and 5 died in 200 mg·kg^-1 gourp; 3 mice were induced SE and 11 died in 250 mg·kg^-1 group; all 14 mice died in 300 mg·kg^-1 group. For modified methods： 6 mice were induced SE, 2 mice were no-SE and 6 mice died in （150＋50）mg·kg^-1 group; 7 mice were induced SE and 7 died in （150＋100）mg·kg^-1 group; 6 mice were induced SE, 3 mice were no-SE and 5 died in （200＋30）mg·kg^-1 gourp; 9 mice were induced SE and 5 mice died in （200＋50）mg·kg^-1 group. CONCLUSION It may be hard to get a suitable dose to establish pilocarpine SE model when using regular single-dose method, and the （200＋50）mg·kg^-1 modified method may be an optimal strategy to establish pilocarpine SE model in mice.