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目的 研究不同剂量托吡酯(TPM)长期应用对幼年慢性癫痫大鼠发作行为及体重的影响。方法 出生后21天大鼠,使用锂一匹罗卡品制作癫痫持续状态(SE)后的慢性癫痫模型;不同剂量的TPM(20mg·kg-1·d-1,40mg·kg-1·d-1,80mg·kg-1·d-1)分2次灌胃给予,连续5周,在此期间每天观察大鼠行为学及体重变化,并比较对照组与各实验组结果的差异。结果 大鼠在腹腔注射匹罗卡品后21～39 min(平均32 min)出现RacineⅣ级或Ⅴ级发作及癫痫持续状态(SE),SE后大鼠出现5～22 d(平均16.5 d)的静默期,其后大鼠进入慢性癫痫发作期,表现为Racine Ⅰ～Ⅲ级的自发反复发作(SRS)。癫痫大鼠长期给予TPM时,其静默期长度无变化,慢性期单位时问内SRS明显减少。癫痫大鼠SE后的5周时体重较对照组减轻;癫癫大鼠TPM治疗组在TPM治疗5周时,其体重较未治疗组减轻。结论 锂-匹罗卡品致大鼠SE后可出现慢性癫痫发作;长期应用TPM可抑制慢性癫痫大鼠的SIRS,对于SE后的慢性癫痫具有明显抗癫痫作用;长期应用TPM可使癫痫大鼠的体重减轻。
Objective To investigate the effects of long-term use of topiramate (TPM) at different doses on seizure behavior and body weight in juvenile chronic epileptic rats. Methods After 21 days of birth, rats were treated with lithium-pilocarpine to make chronic epilepsy model after epileptic seizure (SE). Different doses of TPM (20 mg · kg-1 · d-1, 40 mg · kg-1 · d -1, 80mg · kg-1 · d-1) were given orally twice a day for 5 weeks. During this period, the behavior and body weight of rats were observed. The differences between the control group and the experimental groups were also compared. Results Racine grade Ⅴ or grade Ⅴ seizures and status epilepticus (SE) occurred in 21-39 min (average 32 min) after intraperitoneal injection of pilocarpine in rats. Rats in seizure 5-7 d (mean 16.5 d) During the silent period, rats then entered the chronic epileptic seizure phase, showing spontaneous recurrent episodes (SRS) of grade Ⅰ ~ Ⅲ of Racine. Long-term epileptic rats given TPM, no change in the length of the silent period, chronic unit SRS was significantly reduced. At 5 weeks after epileptic seizure, the body weight of rats in SEP group was lower than that of control group. TPM group of epilepsy rats reduced in weight at 5 weeks after TPM treatment compared with that of untreated group. Conclusion Long-term application of TPM can inhibit the SIRS of chronic epilepsy rats after seizures induced by lithium-pilocarpine in rats, and has obvious antiepileptic effect on chronic epilepsy after SE. Long-term use of TPM can induce epileptic rats Weight loss.