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

摘要:

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。

Abstract:

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.