柴胡疏肝汤对难治性癫痫大鼠脑电图及多药耐药蛋白P-糖蛋白表达的影响

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目的:探讨柴胡疏肝汤对锂-匹罗卡品致难治性癫痫模型大鼠脑电图变化以及多药耐药蛋白P-糖蛋白(P-gp)表达的影响。方法:将制备成功的50只SD难治性癫痫大鼠模型随机分为5组,模型组(B)、丙戊酸钠(VPA)组(C)、柴胡疏肝汤低(D)、中(E)、高(F)剂量组,每组各10只,另有空白对照组(A)10只。柴胡疏肝汤是以柴胡桂枝汤和四物汤为基础方加味煎煮浓缩而成,含生药1 g.mL-1。VPA组用量为0.2 g.kg-1,柴胡疏肝汤低、中、高浓度依次为4.5,9,18 g.kg-1,空白组和模型组给予等量生理盐水。各组均ig给药8周,给药结束后检测各组大鼠脑电图以及海马、颞叶皮层P-gp蛋白的表达。结果:脑电图:A组无痫性波出现,B组出现大量的痫性波,C,D,E,F组能不同程度的减少脑电图的痫性波,以F组最明显。在大鼠海马区、颞叶皮层,Western blotting检测各组P-gp表达,差异有统计学意义(P﹤0.01)。与A组相比,其余各组P-gp表达水平明显增强(P﹤0.01);与B组相比,C组表达水平增加(P﹤0.01),D,E,F组表达水平降低,以F组最明显(P﹤0.01)。结论:VPA明显增强难治性癫痫模型大鼠脑内海马、颞叶皮质P-gp蛋白的表达,柴胡疏肝汤低、中、高剂量均可以降低海马、颞叶皮层P-gp蛋白的表达以及脑电图的痫性放电,以高剂量组明显。 Objective: To investigate the effects of Chaihu Shugan Decoction on electroencephalogram (EEG) and expression of P-glycoprotein (P-gp) in lithium-pilocarpine-induced epilepsy model rats. Methods: Fifty SD rats with intractable epilepsy were randomly divided into five groups: model group (B), VPA group (C), Chaihu Shugan Tang low (D) (E), high (F) dose group, each group of 10, another blank control group (A) 10. Bupleurum liver soup is based on Chaihu Guizhi soup and Siwu Tang-based decoction boiling concentrated, with crude drug 1 g.mL-1. VPA group was 0.2 g.kg-1, Chaihu Shugan Tang low, medium and high concentrations were 4.5,9,18 g.kg-1, the blank group and the model group were given the same amount of saline. The rats in each group were given ig for 8 weeks. After the administration, the expression of P-gp protein in the EEG and hippocampus and temporal cortex of the rats in each group were detected. Results: Electroencephalogram (EEG): There was no epileptic wave in group A, and a large number of epileptic waves appeared in group B, and epileptic waves in groups C, D, E and F were decreased to some extent. In rat hippocampus, temporal cortex and Western blotting, the expression of P-gp in each group was significantly different (P <0.01). Compared with group A, the expression of P-gp was significantly increased in other groups (P <0.01). Compared with group B, the expression of P-gp was increased (P <0.01) F group was the most obvious (P <0.01). Conclusion: VPA can significantly increase the expression of P-gp protein in the hippocampus and temporal cortex in the rat model of intractable epilepsy. In all cases, Chaihu Shugan decoction can reduce the expression of P-gp protein in hippocampus and temporal cortex Epileptiform discharges and EEG seizures were evident at high doses.
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