全蝎醇提物对氯化锂-毛果芸香碱诱导癫癎持续状态模型大鼠海马神经细胞caspase-3表达的影响

Effects of Ethanol Extracts of Scorpion on Caspase-3 Expression in Rat Hippocampus after Lithium-Pilocarpine Induced Status Epilepticus

目的:探讨全蝎醇提物(EES)对氯化锂-毛果芸香碱诱导癫癎持续状态模型鼠的疗效及对癫癎持续状态后海马神经细胞caspase-3表达的影响。方法:156只成年雄性大鼠除6只设为正常对照组外,其余均建立氯化锂-毛果芸香碱癫癎持续状态大鼠模型,造模成功后随机分为模型组、丙戊酸钠干预组和EES低(EESL组)、中(EESM组)、高(EESH组)剂量干预组(均n=30),观察各组大鼠癫癎持续状态发作情况,用免疫组化方法观察各组大鼠癫癎持续状态后6、24、48、72h和7d各时点海马神经细胞caspase-3表达的变化。结果:癫癎持续状态模型鼠的造模成功率为95.2%。经EESM、EESH和丙戊酸钠治疗后,大鼠发作癫癎持续状态级别及持续时间较模型组显著改善(P<0.01)。各观察时点CA1区和CA3区caspase-3阳性细胞数较模型组显著减少(P<0.05),其中以EESH和丙戊酸钠疗效最好(两者疗效相当,P>0.05);EESL疗效不明显,与模型组比差异无统计学意义(P>0.05)。结论:一定剂量的EES能显著对抗癫癎持续状态发作,疗效与caspase-3细胞的减少相对应,说明EES具有抗凋亡作用。对caspase-3表达的抑制可能是其发挥抗凋亡作用的机制之一。

Aim： To explore the effects of ethanol extracts of scorpion （EES） on seizure control for the rat model of status epilepticus （SE） induced by lithium-pilocarpine （Li-Pilo）, and on caspase-3 expression in rat hippocampus after SE. Methods： Experimental SE was induced by lithium-pilocarpine injection in 150 adult male rats, another 6 rats were served as the normal controls. SE rats were randomly divided into Li-Pilo SE-only group（n=30）, VPA （valproate） group（n=30）, low dose of EES group（EESL, n=30）, middle dose of EES group（EESM, n=30） and high dose of EES group（EESH, n=30）. Seizures were monitored with Racine＇s seizure severity scale, caspase-3 expression was observed by immunohistochemistry at 6 h, 24 h, 48 h, 72 h and 7 d after SE. Results： Models of SE were successfully induced in 95.2% rats. Compared with SE-only group, the seizure severity and SE durations were significantly improved （P〈0.01）, and the number of caspase-3 expression neurons in CA 1 and CA3 regions of hippocampus was significantly reduced （P〈0.05） at each time point after treated by EESM, EESH and VPA, especially when treated by EESH and VPA. There was no significant difference between EESH group and VPA group（P〉0.05）, and also no significant difference was observed between the EESL group and the SE-only group（P〉0.05）. Conclusion： EES is efficient to decrease the seizure severity, SE duration and caspase-3 expression of neurons in certain dosage range. It was suggested that EES has anti-apoptotic effects on Li-Pilo SE rats. To inhibit the expression of caspase-3 is probably one of the anti-apoptotic mechanisms of EES.