宁痫颗粒联合卡马西平对难治性癫痫大鼠脑组织MDR1基因表达影响的相关性研究

Research of the Effect of Ninxian Particles Combined with Carbamazepine on Expression of MDR1 in Intractable Epilepsy Rats Brain

目的:采用宁痫颗粒联合卡马西平治疗难治性癫痫大鼠,观察其对大鼠脑组织MDR1基因表达的影响。方法:Wistar雄性大鼠42只,按体质量随机分为假手术组、模型组、卡马西平+宁痫颗粒高(0.03+4.80 g/kg/d)、中(0.03+2.40 g/kg/d)、低剂量组(0.03+1.20 g/kg/d)、宁痫颗粒组(2.40 g/kg/d)和卡马西平组(0.03 g/kg/d),每组6只。采用海马CA3局部注射海人酸制作大鼠癫痫模型,术后第二天予苯妥英钠药物筛选14 d后成功制作难治性癫痫模型。采用荧光定量PCR法检测MDR1。结果:中药组、西药组及中西药联合组与模型组比较,各组的大鼠脑组织的MDR1含量均降低,差异有统计学意义(P<0.01),与卡马西平组比较,中剂量、高剂量宁痫颗粒联合卡马西平组大鼠脑组织MDR1mRNA含量显著降低(P<0.05)。结论:提示卡马西平组、宁痫颗粒及宁痫颗粒联合卡马西平高、中、低剂量组均可以降低MDR1在难治性癫痫大鼠脑组织中的表达;与单纯卡马西平组比较,宁痫颗粒联合卡马西平中、高剂量组能更明显的促使难治性癫痫大鼠脑组织的MDR1mRNA下调。另从实验大鼠症状、行为观察中发现中、高剂量宁痫颗粒联合卡马西平组可明显抑制痫性发作,而宁痫颗粒组和卡马西平组均未能控制癫痫临床发作。

Objective： To observe the effect of Ninxian Particles combined with Carbamazepine（ CBZ） on Expression of MDR1 in Intractable epilepsy rats brain. Methods： Forty-two male Wistar rats were divided randomly into seven group： model group,sham group,Ninxian particles with CBZ high dose group（ 0. 03 ＋ 4. 80 g / kg / d）,medium dose group（ 0. 03 ＋ 2. 40 g / kg / d） and low dose group（ 0. 03 ＋ 1. 20 g / kg / d） groups,Ninxian particles group（ 2. 40 g / kg / d） and CBZ group（ 0. 03 g / kg / d）（ n = 6）.The model rats of epilepsy was induced by inject the kainic acid into rats＇ CA3 areas of hippocampi,Sodium Phenytoin was used on the production for 14 days to screen if it is a successful intractable epilepsy rats model. Fluorescence quantitative PCR（ FQ PCR） was used to detect MDR1 in epilepsy rats brain. Results： The content of MDR1 decreased in those groups,including Ninxian particles group,CBZ medicine group,Ninxian particles with CBZ group and model group（ P〈0. 01）. Compared with CBZ group,the content of MDR1 mRNA decreased significantly in Ninxian particles with CBZ high and medium groups（ P〈0. 05）. Conclusion： CBZ group,Ninxian particles group,and also Ninxian particles high / medium / low dose with CBZ groups,all could decrease MDR1 mRNA in KA rats. Ninxian particles high and medium dose with CBZ groups could reduce increasing MDR1 mRNA in KA intractable epilepsy rats. From this experiment,both Ninxian particles group and CBZ group did less effect on inhibit epileptic seizures,while Ninxian particles with CBZ high and medium groups could reduce it markedly.