改良锂-匹罗卡品大鼠癫痫模型的制作及性别特点

Establishment of modified lithium-pilocarpine-induced epilepsy rat model and gender difference

目的建立稳定可靠的颞叶癫痫动物模型,摸索并证实建模规律。方法选用56只健康SD大鼠,雌雄近半,随机分配为试验组48只,对照组8只氯化锂3 mmol/kg腹腔注射预处理;18～20h后首剂注射匹罗卡品30mg/kg,此后篛隔30分钟注射10mg/kg追加剂量,极量为60 mg/kg,直至出现癫痫持续状态(SE);SE 1 h后地西泮10 mg/kg止痉,2 h后注射生理盐水5 mL/只,2/d,连续2d;SE后次日起灌胃鸡蛋牛奶糊7 mL/只,2/d,连续6 d:观察大鼠行为学改变。对照组大鼠除用等量生理盐水代替匹罗卡品外,其余处理措施均相同。结果大鼠成功点燃44只,病死10只,造模总成功只数为34。雌雄大鼠点燃只数相近,雄鼠病死只数低于雌鼠。结论中等剂量首剂,不超过3次小剂量累加腹腔注射匹罗卡品造模简易有效,可操作性强,效应匀齐。改良护理方法可明显降低病死率,雄鼠较雌鼠更适于造模。

Objective To set up a stable and reliable epilepsy model, and to explore and prove the rules of this method. Methods Healthy Sprague-Dawley rats （n=56） were used in this study, including 30 males and 26 females. They were randomly divided into 2 groups： experimental group （n=48） and control group （n=8）. Pretreated by lithium chloride at a dose of 3 mmol/kg ip, the subjects were injected with pilocarpine 30 mg/kg as first dose after 18-20 h. Then they were administered with low dose pilocarpine （10 mg/kg） every 30 min until status epilepticus （SE） broke out, but maximal dose was 60 mg/kg. SE was interrupted by diazepam （10 mg/kg） after 60 min. Survival rats received injections of 0.9% saline, 5 mL twice every day for 2 d. From the 2nd day after SE, all rats were tube-fed with mixture of egg and milk, 7 mL twice every day for 6 d in succession. The subjects were observed on their behaviors. Results 44 rats of experimental group were kindled by pilocarpine, 10 rats were dead, 34 rats were induced successfully in all. The kindled number of male rats was close to that of the female rats, but less male rats died than female ones did. Conclusion A modified pilocarpine kindling protocol, which consists of modest dose pilocarpine as first administration and at most three times repeated low dose intraperitoneal injections in addition, is a simple and effective access to induce epilepsy rat model. Its merits lie in convenience and equal response. Moderate post-seizure care can reduce mortality rate obviously. Male is more suitable to induce epilepsy model than female.