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

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。

Effect of Chaihu ShuganTang on Electroencephalogram and Expression of Multidrug Resistance Protein P-glycoprotein of Refractory Epilepsy

Objective: To investigate the effect of Chaihu Shugan Tang on EEG and expression of multidrug resistance protein P-gp of refractory epilepsy rats induced by licl-pilocarpine. Method: Except for blank control group(A),50 Sprague-Dawley refractory epilepsy rats were randomly divided into five groups: model group(B group),VPA group(C group),low,middle,high dose of Chaihu Shugan Tang groups (D,E,F group). Chaihu Shugan Tang was decocted and concentrated into 1g crude drug/mL. C group is administrated for 0.2 g ·kg^-1, D,E,F group is 4.5,9,18 g ·kg^-1,the same amount of saline was given to A,B group. After the intragastirc administration for 8 weeks each group, EEG was recorded and the protein P-gp was detected in rat hippocampus and temporal cortex in each group. Result: There was no epileptic wave in A group,but much more epileptic wave in B group. Epileptic wave were decreased in C,D,E,F groups compared with B group. Expression of P-gp by Western blotting was different in each group ( P <0.01). Conclusion :VPA increases expression of multidrug resistance protein P-gp in rat hippocampus and temporal cortex. Chaihu Shugan Tang decreases expression of P-gp and epileptic wave. High dose of Chaihu Shugan Tang is the most efficient.