α细辛醚对耐药性癫痫模型大鼠脑组织中P糖蛋白与多药耐药基因表达的影响  

Influences of α-asarone on the Expression of P-glycoprotein and Multidrug Resistance Genes in Brain Tissues of Drug-resistant Epileptic Model Rats

作　　者：袁斯远 王潇慧 孙江燕 刘金民[2] YUAN Siyuan;WANG Xiaohui;SUN Jiangyan;LIU Jinmin(The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China;Dong Fang Hospital of Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学第三附属医院,北京100029 [2]北京中医药大学东方医院,北京100078

出　　处：《中西医结合心脑血管病杂志》2019年第21期3322-3325,共4页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金(No.81774277)

摘　　要：目的观察α细辛醚对戊四氮所致耐药性癫痫模型大鼠海马与皮层中P糖蛋白(P-gp)与多药耐药基因1a(Mdr1a)mRNA表达的影响。方法将8周龄Wistar雄性大鼠隔日腹腔注射亚剂量的戊四氮(30 mg/kg),持续30 d,按Racine分级将注射戊四氮后大鼠癫痫发作进行分级,连续3次及以上出现Ⅴ级发作者,视为癫痫造模成功,用于筛选耐药性癫痫大鼠。将癫痫造模成功的大鼠,灌服卡马西平(125 mg/kg)与苯妥英钠(62.5 mg/kg)1 h后,注射相同剂量的戊四氮,观察大鼠癫痫发作级别,动物筛选实验持续1周,连续3次出现5级发作者,视为耐药性癫痫大鼠模型。将耐药性癫痫大鼠随机分为α细辛醚低、高剂量组与模型组;另设正常组,干预3周后取材,使用Western blot技术检测大鼠海马与皮层中P-gp表达;使用real time PCR技术检测大鼠海马与皮层中Mdr1a mRNA的表达。结果与正常组相比,模型组大鼠海马与皮层组织中P-gp和Mdr1a mRNA均明显升高(P<0.05);α细辛醚低、高剂量组大鼠海马与皮层中P-gp与Mdr1a mRNA的表达均较模型组降低,其中α细辛醚高剂量组与模型组比较差异有统计学意义(P<0.05)。结论高剂量的α细辛醚能明显下调模型大鼠海马与皮层中P-gp与Mdr1a mRNA的表达,扭转P-gp介导的癫痫耐药性。Objective To investigate the effects ofα-asarone on the expression of P-glycoprotein and multidrug resistance 1α(Mdr1α)mRNA in the cortex and hippocampus of the drug-resistant epilepsy rats.Methods The 8-week-old Wistar male rats were intraperitoneally injected with sub dose pentaerythritol(30 mg/kg)every other day for 30 days.According to Racine classification,the epileptic seizures of the rats after injection of pentaerythritol were classified and the rats with 3 or more consecutive episodes of grade 5 were regarded as successful epileptic modeling for screening drug-resistant epileptic rats.Rats with successful epilepsy modeling were injected with carbamazepine(125 mg/kg)and phenytoin(62.5 mg/kg)for 1 h,and the same dose of pentaerythritol was injected to observe the grade of seizures in the rats.The animal screening experiment lasted 1 week,and the rats with 3 consecutive episodes of grade 5 were considered as drug-resistant epilepsy rat models.Drug-resistant epileptic rats were randomly divided into the low-doseα-asarone group,high-doseα-asarone group,model group and normal group.After 3 weeks of intervention,western blot was used to detect p-gp expression in the hippocampus and cortex of rats.The expression of Mdr1a mRNA in the hippocampus and cortex of rats was detected by real-time PCR.Results Compared with data in the normal group,P-gp,and Mdr1a mRNA levels in the hippocampal and cortical tissues of the model group were significantly increased(P<0.05).The expressions of P-gp and Mdr1a mRNA in the hippocampal and cortical tissues of the low-dose and high-doseα-asarone group were lower than those in the model group,and the difference between the high-dose and model groups was statistically significant(P<0.05).Conclusion The expression of P-gp and Mdr1a mRNA in the hippocampus and cortex of model rats was significantly down-regulated by the high dose ofα-asarone,and the P-gp-mediated epilepsy drug resistance was reversed.

关 键 词：耐药性癫痫 α细辛醚 P糖蛋白 多药耐药基因1a 戊四氮 脑组织 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]