柴胡皂苷a对难治性癫痫大鼠多药耐药蛋白P-糖蛋白表达的影响

Effect of Saikosaponin a on Expression of Multidrug Resistance Protein P-glycoprotein in Refractory Epilepsy Rats

摘要:

目的: 研究柴胡皂苷a(SSa)对氯化锂-匹鲁卡品致难治性癫痫模型大鼠多药耐药蛋白P-糖蛋白(P-gp)表达的影响。 方法: 将制备成功的30只SD难治性癫痫大鼠随机分为5组,丙戊酸钠(VPA)组以VPA 200 mg·kg^-1灌胃给药,SSa低、中、高剂量组分别ip SSa 0.54,1.09,2.18 mg·kg^-1,空白对照组(A)和模型组(B)均等容积生理盐水ig,各组连续给药8周后用Western blotting 检测各组大鼠海马、颞叶皮层P-gp的表达。 结果: 在大鼠海马、颞叶皮层,各组P-gp的表达,差异有统计学意义(P<0.001)。与空白对照组相比,其余各组P-gp表达水平明显增强(P<0.05); 与模型组相比,VPA 200 mg·kg^-1组表达水平增加(P<0.05),SSa 3个剂量组表达水平降低,以SSa高剂量组最明显(P<0.05)。 结论: SSa低、中、高剂量均可降低大鼠颞叶皮层、海马区P-gp的表达,其效果成剂量依赖性,以高剂量组效果明显。

Abstract:

Objective: To investigate the effect of saikosaponin a(SSa) on expression of multidrug resistant protein P-glycoprotein(P-gp) in refractory epilepsy rats induced by licl-pilocarpine. Method: Except for the blank control group (A),thirty SD refractory epilepsy rats were randomly divided into 5 groups, namely,sodium valproate(VPA) group C (200 mg·kg^-1,ig),low,middle and high dose of SSa group(0.54, 1.09, 2.18 mg·kg^-1,ip). The model group (B) and group A received the same amount of saline. At the end of treatment for 8 weeks, the expression of P-gp in rat hippocampus and temporal lobe cortex was detected by Western blotting. Result: The P-gp expressed in the rat hippocampus and temporal cortex in different groups had statistically significant difference(P<0.001). Compared with group A, the expression of P-gp were increased significantly in the other groups(P<0.05);the expression was increased in group C(P<0.05),but decreased in group D,E and F when compared with group B. The reduction of expression was most apparent in group E(P<0.05). Conclusion: SSa can reduce the expression of P-gp in hippocampus and temporal cortex with a slightly dose-dependent manner,which may be one of the anticonvulsant mechanisms of SSa.