柴贝止痫汤及α细辛醚对难治性癫痫大鼠脑内P-gp表达及卡马西平含量的影响

Effects of Chaibei Zhixian Decoction and α-asarone on the P-gp expression and carbamazepine content in the brain of intractable epileptic rats

目的:观察柴贝止痫汤及其入血成分α细辛醚对难治性癫痫(IE)大鼠脑内P-糖蛋白(P-gp)表达及卡马西平(CBZ)含量的影响。方法:采用侧脑室注射海人酸法建立IE大鼠模型。分为模型组、西药组、中西药组、α细辛醚+CBZ组,设假手术组,给药时间60d。以Western Blot、RT-PCR、LC-MS对比脑内海马P-gp和Mdr1b mRNA表达及脑内CBZ、10,11环氧化卡马西平(CBZE)含量。结果:模型组及西药组大鼠海马中P-gp和Mdr1b mRNA含量显著高于假手术组(P<0.05);中西药组及α细辛醚+西药组大鼠海马中P-gp和Mdr1b mRNA含量显著低于模型组、西药组(P<0.01,P<0.05)。中西药组和α细辛醚+西药组脑内CBZE含量显著高于西药组(P<0.01)。结论:柴贝止痫汤及α细辛醚可能降低IE大鼠海马Mdr1b mRNA/P-gp表达,促进CBZ和CBZE入脑,对CBZE作用突出。

Objective:To observe the effect of Chaibei Zhixian Decoction andα-asarone on P-gp expression and carbamazepine(CBZ)content in the brain of intractable epileptic rats.Methods:Epilepsy rat models were established by injecting kainic acid in the lateral ventricle.Rats were divided into model group,western medicine group,Chinese and western medicine group,α-asarone+CBZ group and sham operation group.Rats were treated with corresponding medicine for 60 days.Then comparing the expression of P-gp,Mdr1b mRNA and the content of CBZ,10,11-epoxidation of carbamazepine(CBZE)by Western Blot,reverse transcription-polymerase chain reaction(RT-PCR)and liquid chromatograph-mass spectrometer(LC-MS).Results:The content of P-gp and Mdr1b mRNA in the hippocampus of the rats were higher in the model group than that in the sham operation group(P<0.05).The content in Chinese and western medicine group andα-asarone+CBZ group were lower than that of the model group and western medicine group(P<0.01,P<0.05).The content CBZE in the brain was higher in the Chinese and western medicine group and theα-asarone+CBZ group than that in the western medicine group(P<0.01).Conclusion:Chaibei Zhixian Decoction andα-asarone can reduce the expression of Mdr1b mRNA/P-gp in the hippocampus of rats,and promote the entry of CBZ and CBZE into the brain,especially the prominent effect on CBZE.