左乙拉西坦对癫癎大鼠海马组织中NCAM和GAP-43 mRNA表达的影响

Effects of levetiracetam on the expression of NCAM and GAP-43 mRNA in the hippocampus of rats with epilepsy

目的通过氯化锂-匹罗卡品(Li-PILO)诱导的癫癎大鼠模型,观察左乙拉西坦(LEV)对大鼠海马组织中神经细胞黏附分子(NCAM)和生长相关蛋白-43(GAP-43)mRNA的表达变化,为阐明LEV的抗癫癎机制及其剂量效应提供实验依据。方法将48只Wistar大鼠随机分成对照组、Li-PILO组(模型组)、150 mg/kg LEV组和300 mg/kg LEV组,每组12只。对LEV组大鼠予以LEV灌胃,首次灌胃时间为癫癎持续状态后6 h,剂量分别为150和300 mg/kg,每日一次,持续2周。Real-time PCR法测定各组大鼠海马组织中NCAM和GAP-43的mRNA表达。结果模型组大鼠海马NCAM及GAP-43的mRNA表达水平明显高于正常对照组(P<0.05),150 mg/kg LEV组和300 mg/kg LEV组明显低于模型组(P<0.05),其中300 mg/kg LEV组明显低于150 mg/kg LEV组(P<0.05)。结论 Li-PILO诱导癫癎大鼠海马NCAM和GAP-43 mRNA表达上调,LEV能够抑制NCAM和GAP-43 mRNA的表达,其抑制效果与剂量有关。

Objective This study explored the effects of levetiracetam（LEV） on the expression of nerve cell adhesion molecule（NCAM） and growth-associated protein 43（GAP-43） mRNA in the hippocampus of rats with epilepsy induced by lithium-pilocarpine（Li-PILO） in order to provide a basis for investigating the antiepileptic mechanism of LEV and its doseresponse.Methods Forty-eight Wistar rats were randomly divided into a normal control,a Li-PILO model and two LEV treatment groups（LEV： 150 and 300 mg/kg）（n=12 each）.The LEV treatment groups received LEV by intragastric administration 6 hrs after status epilepticus（once daily for 2 two weeks）.The expressions of NCAM and GAP-43 mRNA in the hippocampus was determined by real-time PCR.Results The expression of NCAM and GAP-43 mRNA in the Li-PILO model group was significantly higher than in the normal control group（P〈0.05）.LEV treatment of 150 and 300 mg/kg significantly decreased the expression of NCAM and GAP-43 mRNA compared with the Li-PILO model group（P〈0.05）.The LEV treatment group at the dose of 300 mg/kg showed significantly lower expression of NCAM and GAP-43 mRNA than the 150 mg/kg LEV treatment group（P〈0.05）.Conclusions Li-PILO can up-regulate the expressions of NCAM and GAP-43 mRNA in the hippocampus of rats with epilepsy.LEV can inhibit the expression of NCAM and GAP-43 mRNA and the effect is associated with the dose of LEV.