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目的:了解雌激素受体调节剂克罗米酚(clomiphene citrate,CC)对海人藻酸(kainic acid, KA)致癎大鼠癫癎发作行为的影响。方法:健康雌性SD大鼠40只,均行双侧卵巢切除术,术后第八天将动物随机分4组:茶油对照组(OIL组)、KA组、雌二醇(E2)+KA组、E2+CC+KA组,每组10只。 OIL组、KA组连续5天腹腔注射茶油;E2+KA组连续5天腹腔注射E2(20mg/kg,10mg/ml);E2+CC +KA组连续5天腹腔注射E2和CC(2mg/kg,2mg/ml),最后一次打药结束1 h后,致癎各组大鼠(KA 组、E2+KA组、E2+CC+KA组)经腹腔注射KA(10mg/kg,2mg/ml),OIL组腹腔注射生理盐水后,连续观察大鼠2 h的行为改变。记录癎样发作的潜伏期、出现重型发作的时间以及发作程度。结果:E2+ CC+KA组的癫癎发作潜伏期为61.75±19.04 min,较E2+KA组的潜伏期23.8±6.03 min延长,且出现重型癫癎发作的时间晚,为50.20±20.37 min,而E2+KA组出现重型癫癎发作时间平均为30.70 ±13.58 min,两组比较差异有显著意义(P<0.05)。致癎2 h后,致癎各组大鼠的癫癎发作Racine分级比较差异显著意义(P>0.05)。结论:CC有拮抗雌激素的致癎作用,延缓癫癎的发作。
Objective: To investigate the effect of estrogen receptor modulator clomiphene citrate (CC) on epileptic seizures induced by kainic acid (KA) in rats. Methods: Forty female Sprague-Dawley rats were randomly divided into 4 groups: Oli group, KA group, estradiol (E2) + KA Group, E2 + CC + KA group, 10 rats in each group. OEL group and KA group were intraperitoneally injected with tea oil for 5 days. E2 + KA group was intraperitoneally injected with E2 (20mg / kg, 10mg / ml) for 5 days and E2 + CC + KA group kg, 2mg / ml). After 1 h of the last dose, KA (10mg / kg, 2mg / ml) was given intraperitoneally to rats in each group (KA group, E2 + KA group and E2 + CC + KA group) , OIL group after intraperitoneal injection of saline, continuous observation of rats 2 h behavior change. Record 癎-like episodes of incubation period, the occurrence of heavy attacks and the extent of the attack. Results: The latency of epileptic seizure in E2 + CC + KA group was 61.75 ± 19.04 min, which was longer than that of E2 + KA group in 23.8 ± 6.03 min, and the onset of severe epileptic seizure was late 50.20 ± 20.37 min, while the average onset time of severe epileptic seizures in E2 + KA group was 30.70 ± 13.58 min, with significant difference between the two groups (P <0.05). After 2 hours, the Racine scores of epileptic seizures in rats in each group were significantly different (P> 0.05). CONCLUSION: CC antagonizes estrogen-induced neurotoxicity and delays the onset of epilepsy.