Effects of Chaibei Zhixian Decoction（柴贝止痫汤） and its Constituents Migrating to Blood Saikosaponin a on Distribution of Carbamazepine in Brain in Epilepsy Model Rats

SUN Jiangyan; LIU Chongchong; YUAN Siyuan; WANG Xiaohui; LIU Jinmin

doi:10.13288/j.11-2166/r.2019.08.014

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Effects of Chaibei Zhixian Decoction（柴贝止痫汤） and its Constituents Migrating to Blood Saikosaponin a on Distribution of Carbamazepine in Brain in Epilepsy Model Rats

更新时间：2021-11-10

- Effects of Chaibei Zhixian Decoction（柴贝止痫汤） and its Constituents Migrating to Blood Saikosaponin a on Distribution of Carbamazepine in Brain in Epilepsy Model Rats
- Journal of Traditional Chinese Medicine Vol. 60, Issue 8, Pages: 689-695(2019)
- 作者机构：
  
  1. 北京中医药大学第三附属医院
  2. 北京中医药大学东方医院
  3. 青岛市海慈医疗集团
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2019.08.014
  CLC： R-332;R285.5
- Published：2019
- 稿件说明：
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[1]孙江燕,刘冲冲,袁斯远,王潇慧,刘金民.柴贝止痫汤及其主要入血成分柴胡皂苷a对癫痫模型大鼠卡马西平脑内分布的影响[J].中医杂志,2019,60(08):689-695.

SUN Jiangyan, LIU Chongchong, YUAN Siyuan, et al. Effects of Chaibei Zhixian Decoction（柴贝止痫汤） and its Constituents Migrating to Blood Saikosaponin a on Distribution of Carbamazepine in Brain in Epilepsy Model Rats[J]. Journal of Traditional Chinese Medicine2019, 60(8): 689-695.
[1]孙江燕,刘冲冲,袁斯远,王潇慧,刘金民.柴贝止痫汤及其主要入血成分柴胡皂苷a对癫痫模型大鼠卡马西平脑内分布的影响[J].中医杂志,2019,60(08):689-695. DOI： 10.13288/j.11-2166/r.2019.08.014.

SUN Jiangyan, LIU Chongchong, YUAN Siyuan, et al. Effects of Chaibei Zhixian Decoction（柴贝止痫汤） and its Constituents Migrating to Blood Saikosaponin a on Distribution of Carbamazepine in Brain in Epilepsy Model Rats[J]. Journal of Traditional Chinese Medicine2019, 60(8): 689-695. DOI： 10.13288/j.11-2166/r.2019.08.014.

摘要

目的观察柴贝止痫汤及柴胡皂苷a治疗难治性癫痫的可能作用机制。方法 88只大鼠随机分为空白组12只及模型组、卡马西平组、柴贝止痫汤+卡马西平组、柴胡皂苷a+卡马西平组19只。除空白组外

其余各组采用侧脑室注射海人酸制备癫痫大鼠模型。卡马西平组给予卡马西平混悬液0.75 ml/（100 g·d）

柴贝止痫汤+卡马西平组给予柴贝止痫汤0.5 ml/（100 g·d）和卡马西平混悬液0.75 ml/（100 g·d）

柴胡皂苷a+卡马西平组给予柴胡皂苷a混悬液0.25 ml/100 g和卡马西平混悬液0.75 ml/100 g

模型组及空白组给予等量羧甲基纤维素钠混悬液。给药60天后比较各组海马P糖蛋白、Mdr1a mRNA表达及全脑卡马西平（CBZ）、1011-环氧化卡马西平（CBZE）含量。结果与空白组比较

模型组海马P糖蛋白表达升高（P<0.05）;与模型组比较

卡马西平组、柴胡皂苷a+卡马西平组海马P糖蛋白表达差异无统计学意义（P>0.05）

柴贝止痫汤+卡马西平组海马P糖蛋白表达降低（P<0.05）;与卡马西平组比较

柴贝止痫汤+卡马西平组和柴胡皂苷a+卡马西平组海马P糖蛋白表达均降低（P<0.05）

柴贝止痫汤+卡马西平组和柴胡皂苷a+卡马西平组海马P糖蛋白表达差异无统计学意义（P>0.05）。模型组Mdr1a mRNA表达较空白组升高。卡马西平组的Mdr1a mRNA表达高于空白组（P<0.05）

空白组、模型组MDR1a mRNA表达分别为卡马西平组的0.36倍、0.87倍。柴贝止痫汤+卡马西平组较卡马西平组Mdr1a含量降低（P<0.01）

为卡马西平组的0.14倍。与卡马西平组比较

柴贝止痫汤+卡马西平组CBZE含量升高（P<0.01）

柴胡皂苷a+卡马西平组CBZE含量降低（P<0.01）

且柴贝止痫汤+卡马西平组和柴胡皂苷a+卡马西平组CBZ差异无统计学意义（P>0.05）;与柴贝止痫汤+卡马西平组比较

柴胡皂苷a+卡马西平组CBZ、CBZE含量均降低（P<0.01）。结论柴贝止痫汤联合卡马西平可降低癫痫模型大鼠海马Mdr1a/P糖蛋白表达

促进CBZ、CBZE入脑

对CBZE作用突出

柴胡皂苷a在其中不发挥主要作用。

Abstract

Objective To observe the possible mechanism of Chaibei Zhixian Decoction（ CBZXD

柴贝止痫汤）and Saikosaponin a（ SSa） in treating intractable epilepsy. Methods A total of 88 rats were randomly divided into blank group of 12 rats and every 19 rats for model group

carbamazepine（ CBZE） group

the CBZXD + CBZE group

and the saikosaponin a + CBZE group. Except for the blank group

other groups used the lateral ventricle injection of kainate to prepare a rat model of epilepsy. The CBZE group was given CBZE suspension 0. 75 ml/（ 100 g·d）. The CBZXD + CBZE group was given CBZXD 0. 5 ml/（ 100 g·d） and CBZE suspension 0. 75 ml/（ 100 g·d）.The saikosaponin a + CBZE group was given saikosaponin a suspension 0. 25 ml/100 g and CBZE suspension0. 75 ml/100 g. The model group and the blank group were given the same amount sodium carboxymethylcellulose suspension. After 60 days of administration

the expression of P-glycoprotein

Mdr1 a mRNA and the content of whole brain carbamazepine（ CBZ） and 10 11-epoxidized CBZE were compared. Results Compared with the blank group

the expression of P-glycoprotein in the hippocampus of the model group was increased（ P < 0. 05）. Compared with the model group

the expression of P-glycoprotein in the hippocampus of the CBZE group

saikosaponin a + carbazepine group was not statistically significant（ P > 0. 05）. The expression of P-glycoprotein in hippocampus of CBZXD + CBZE group was decreased（ P < 0. 05）. Compared with CBZE group

the expression of P-glycoprotein in hippocampus of CBZXD + CBZE group and saikosaponin a + CBZE group was decreased（ P < 0. 05）. There was no significant difference in the expression of P-glycoprotein in hippocampus between CBZXD + CBZE group and saikosaponin a + CBZE group（ P > 0. 05）. Mdr1 a mRNA expression in the model group was increased compared with that in the blank group. The expression of Mdr1 a mRNA in CBZE group was higher than that in the blank group（ P <0. 05）. The expression of MDR1 a mRNA in blank group and model group was 0. 36 times and 0. 87 times higher than that in CBZE group. The content of Mdr1 a in the CBZXD + CBZE group was decreased when compared with that in the CBZE group（ P < 0. 01）

which was 0. 14 times higher than that in the CBZE group. Compared with CBZE group

CBZE content in CBZXD + CBZE group was increased（ P < 0. 01）. CBZE content in saikosaponin a +CBZE group was decreased（ P < 0. 01）

and there was no significant difference in CBZ between CBZXD + CBZE group and saikosaponin a + CBZE group（ P > 0. 05）. Compared with CBZXD + CBZE group

saikosaponin a +CBZE group

the content of CBZ

CBZE was reduced（ P < 0. 01）. Conclusion CBZXD combined with CBZE can reduce the expression of Mdr1 a/P glycoprotein in hippocampus of rats with epilepsy

promote CBZ and CBZE into the brain

and play an important role in CBZE. The saikosaponin a dose not play a major role in the above process.

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