摘要
目的难治性癫痫(refractory epilepsy,RE)的发生机制尚不明确。现已明确多药耐药相关蛋白(multidrugresistance associated protein,MRP)1与某些肿瘤耐药有关。为了探讨该蛋白是否与癫痫的多药耐药相关,本研究利用大鼠癫痫模型观察癫痫发作对大鼠脑MRP1 mRNA表达的影响及左乙拉西坦(Levetiracetam,LEV)和托吡酯(Topiramate,TPM)的作用。方法通过脑立体定向技术,将海人酸(kainic acid,KA)1.5μg(3μl)注射至SD大鼠海马,制作癫痫模型。对照组大鼠海马注射3μl等渗盐水。建立模型3 d后,将癫痫组和对照组大鼠各15只随机分为LEV、TPM和NS亚组分别给予LEV(50 mg/kg)、TPM(40 mg/kg)和等体积NS灌胃,1次/d,共30 d。用荧光定量RT-PCR测定大鼠颞叶、海马MRP1 mRNA表达水平,并进行定量分析。结果各组癫痫大鼠颞叶、海马MRP1 mRNA表达与相应非癫痫组相比呈增高趋势,但差异无统计学意义。非癫痫或癫痫大鼠各处理组间颞叶或海马MRP1 mRNA表达水平总体差异均无统计学意义。结论病程为1个月的慢性癫痫大鼠脑内MRP1 mRNA表达无明显增加,TPM、LEV不影响正常和癫痫大鼠脑MRP1 mRNA的表达。
Objective The pathogenesis of refractory epilepsy （RE） is not yet understood. Multidrug resistance associated protein 1 （ MRP1 ） has been shown to correlate with the resistance to some anticancer drugs. Does MRP1 also play a role in the resistance to antiepileptic drugs？ The aim of this study is to investigate the influence of spontaneous seizures, Levetiracetam （LEV） and Topiramate （TPM） on the MRP1 mRNA expression in the brain of chronic epileptic rats. Methods Epileptic rat models （n = 15） were made by stereotaxic injection of 1.5 μg （3 μl） kainic acid into the hippocampus of male SD rats, and the control rats （ n = 15 ） given 3 μl normal saline （NS） in the same manner. Both the models and controls were randomized into subgroups of TPM, LEV and NS to receive oral TPM （50 mg/kg） , LEV （40 mg/kg） and NS at an identical dose once daily for 30 days. Fluorescent quantitative RT-PCR was used to detect the expression of MRP1 mRNA in the temporal lobe and hippocampus of the rats. Results The expression of MRP1 mRNA in the hippocampus and temporal lobe of the epileptic rats was higher than that in the corresponding controls, but with no statistically significant difference. Nor were any significant differences observed in the level of MRP1 mRNA in hippocampus or temporal lobe among the TPM, LEV and NS subgroups either in the control or in the epilepsy group. Conclusion The expres-sion of MRP1 mRNA is not obviously up-regulated in the brain of the rats with 1 - month chronic epilepsy. TPM and LEV do not significantly change the level of MRP1 mRNA in the brain of either normal or epileptic rats.
出处
《医学研究生学报》
CAS
2010年第2期145-149,共5页
Journal of Medical Postgraduates
基金
南京市医学科技发展重大项目(2007-0211)
