中药柴贝止痫汤对海人酸致痫模型大鼠脑组织中P-糖蛋白和MDR1表达的影响
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摘要
目的:观察柴贝止痫汤、卡马西平、柴贝止痫汤与卡马西平联用3种不同干预对海人酸致痫模型大鼠P-糖蛋白(P-gp)和MDR1表达的影响。方法:采用侧脑室注射海人酸法建立癫痫持续状态后慢性难治性癫痫大鼠模型。随机分为模型组、西药组、中药组、中西药组,另设正常组、假手术组。西药组、中药组、中西药组分别予卡马西平、柴贝止痫汤、柴贝止痫汤联合卡马西平治疗;正常组、假手术组、模型组予0.9%氯化钠溶液,持续干预2个月。干预结束后,摘取大鼠新鲜海马组织,Western blot及Real-time PCR法检测各组大鼠海马P-gp及编码基因MDR1a/1b mRNA水平。结果:与假手术组比较,模型组和西药组P-gp表达、MDR1a/1b mRNA转录水平显著升高(P<0.01,P<0.05)。与模型组比较,中药组和中西药组P-gp表达降低(P<0.05)。与西药组比较,中药组和中西药组P-gp表达显著降低(P<0.05)、中西药组MDR1a/1b mRNA转录水平显著降低(P<0.05)。结论:柴贝止痫汤能够抑制海人酸致痫模型大鼠P-gp表达,这可能是通过对MDR1a/1b mRNA转录水平的影响实现。
Objective: To investigate the effects of Chaibei Zhixian Decoction, Carbamazepine, and combinating Carbamazepine with Chaibei Zhixian decoction on the expression of P-glycoprotein(P-gp) and MDR1 in intractable epilepsy model. Methods: Chronic IE rat models were made by injecting kainic acid in intracerebroventricular, which were divided into model group, western medicine group, Chinese medicine group, Chinese and western medicine group randomly. And normal group, sham operation group were set up. Western medicine group was treated with Carbamazepine, Chinese medicine group was treated with Chaibei Zhixian Decoction, Chinese and western medicine group was treated with both Carbamazepine and Chaibei Zhixian Decoction. Normal group, sham operation group and model group were treated with saline for 2 months. The expression of P-gp and MDR1 a/1 b mRNA were determined by Western blot and Real time PCR. Results: Compared with the sham operation group, the expression of P-gp, MDR1 a/1 b mRNA of model group and western medicine group were higher(P<0.01, P<0.05). Compared with the model group, the expression of P-gp of Chinese medicine group, Chinese and western medicine group were lower(P<0.05). Compared with the western medicine group, the expression of P-gp of Chinese medicine group, Chinese and western medicine group were lower(P<0.05), the expression of MDR1 a/1 b mRNA of Chinese and western medicine group were lower(P<0.05). Conclusion: Chaibei Zhixian Decoction can reduce the expression of intractable epilepsy, which may be did by making effect on MDR1 a/1 b mRNA transcription levels.
Objective: To investigate the effects of Chaibei Zhixian Decoction, Carbamazepine, and combinating Carbamazepine with Chaibei Zhixian decoction on the expression of P-glycoprotein(P-gp) and MDR1 in intractable epilepsy model. Methods: Chronic IE rat models were made by injecting kainic acid in intracerebroventricular, which were divided into model group, western medicine group, Chinese medicine group, Chinese and western medicine group randomly. And normal group, sham operation group were set up. Western medicine group was treated with Carbamazepine, Chinese medicine group was treated with Chaibei Zhixian Decoction, Chinese and western medicine group was treated with both Carbamazepine and Chaibei Zhixian Decoction. Normal group, sham operation group and model group were treated with saline for 2 months. The expression of P-gp and MDR1 a/1 b mRNA were determined by Western blot and Real time PCR. Results: Compared with the sham operation group, the expression of P-gp, MDR1 a/1 b mRNA of model group and western medicine group were higher(P<0.01, P<0.05). Compared with the model group, the expression of P-gp of Chinese medicine group, Chinese and western medicine group were lower(P<0.05). Compared with the western medicine group, the expression of P-gp of Chinese medicine group, Chinese and western medicine group were lower(P<0.05), the expression of MDR1 a/1 b mRNA of Chinese and western medicine group were lower(P<0.05). Conclusion: Chaibei Zhixian Decoction can reduce the expression of intractable epilepsy, which may be did by making effect on MDR1 a/1 b mRNA transcription levels.
引文
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[2]Ngugi A K,Bottomley C,Kleinschmidt I,et al.Estimation of the burden of active and life-time epilepsy:a meta-analytic approach.Epilepsia,2010,51(5):883-990
[3]Dalic L,Cook M J.Managing drug-resistant epilepsy:challenges and solutions.Neuropsychiatr Dis Treat,2016,12(12):2605-2616
[4]Vogelgesang S,Kunert-Keil C,Cascorbi I,et al.Expression of multidrug transporters in dysembryoplastic neuroepithelial tumors causing intractable epilepsy.Clin Neuropathol,2004,23(5):223-231
[5]郑香春,李淑芳,刘金民.柴贝止痫汤单药及合并用药治疗难治性癫痫临床观察.天津中医药,2012,29(3):224-227
[6]Mukhametov A,Raevsky O A.On the mechanism of substrate/non-substrate recognition by P-glycoprotein.J Mol Graph Model,2017,71(7):227-232
[7]GoasdouéK,Miller S M,Colditz P B,et al.The blood-brain barrier:protecting the developing fetal brain.Placenta, 2016,6,Pii:S0143-4004
[8]郑兴珍,武士京.难治性癫痫的耐药性与多药耐药基因的研究进展.神经疾病与精神卫生,2008,8(1):74-77