平肝止痫复方联合卡马西平对难治性癫痫大鼠海马及颞叶皮质区MRP_(1)、P-gp表达的影响  

Effect of Pinggan Zhixian Compound Combined with Carbamazepine on the Expression of MRP_(1) and P-gp in Hippocampus and Temporal Lobe Cortex of Refractory Epilepsy Rats

作　　者：安运佳 王强 钱忆家 薛红 李若照 娄金波 刘运权 AN Yun-jia;WANG Qiang;QIAN Yi-jia;XUE Hong;LI Ruo-zhao;LOU Jin-bo;LIU Yunquan(Guizhou University of Traditional Chinese Medicine,Guiyang 550003,China;The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550002,China)

机构地区：[1]贵州中医药大学,贵州贵阳550003 [2]贵州中医药大学第二附属医院,贵州贵阳550002

出　　处：《云南中医中药杂志》2021年第4期67-72,共6页Yunnan Journal of Traditional Chinese Medicine and Materia Medica

基　　金：国家自然科学地区基金项目(81760857);贵州省科学技术基金项目(黔科合J字[2014]2042号)。

摘　　要：目的探讨平肝止痫复方联合卡马西平对难治性癫痫模型大鼠海马及颞叶皮质区多药耐药相关蛋白1(MRP_(1))、P糖蛋白(P-gp)表达的影响。方法选择Wistar大鼠,采用颅内注射海人酸建立难治性癫痫大鼠模型,随机分为假手术组、模型组、卡马西平组(0.03 g/kg),平肝止痫复方组(4.80 g/kg),高、中、低剂量平肝止痫复方+卡马西平组(9.60+0.03 g/kg,4.80+0.03 g/kg,2.40+0.03 g/kg)。假手术组、模型组采用等体积蒸馏水灌胃,各组连续给药4周,RT-PCR检测海马及颞叶皮质区MRP_(1)、P-gp mRNA的表达;Western Blot检测(WB检测)海马及颞叶皮质区MRP_(1)、P-gp蛋白的表达。结果与假手术组比较,模型组海马区及颞叶皮质区的MRP_(1)、P-gp mRNA含量及蛋白的表达均明显升高(P<0.01);与模型组比较,平肝止痫复方联合卡马西平用药均能显著降低海马区及颞叶皮质区MRP_(1)、P-gp mRNA含量及蛋白的表达(P<0.01,P<0.05);与卡马西平组比较,平肝止痫复方联合卡马西平用药较好,其作用效果与给药剂量高低呈正相关。结论平肝止痫复方联合卡马西平能够显著降低难治性癫痫大鼠MRP_(1)、P-gp表达水平,逆转和降低海马区MRP_(1)、P-gp蛋白的表达可能是平肝止痫复方联合卡马西平抗耐药性癫痫作用机制之一。Objective:To Study the effect of Pinggan Zhixian Compound combined with carbamazepine on the expression of multi-drug resistance related protein 1(MRP_(1))and P-glycoprotein(P-gp)in the hippocampus and temporal lobe cortex of refractory epilepsy model rats.Methods:Wistar rats were selected and intracranial injection of kainic acid was used to establish a refractory epilepsy rat model.The rats were randomly divided into sham operation group,model group,carbamazepine group(0.03 g/kg),and Pinggan Zhixian Compound group(4.80 g/kg),high,medium,and low-dose Pinggan Zhi-epilepsy compound+carbamazepine group(9.60+0.03 g/kg,4.80+0.03 g/kg,2.40+0.03 g/kg).The sham operation group and the model group were given intragastric administration with equal volume of distilled water.Each group was given continuous administration for 4 weeks.RT-PCR was used to detect the expression of MRP_(1) and P-gp mRNA in the hippocampus and temporal lobe cortex and Western Blot used to detect the hippocampus and temporal Expression of MRP_(1) and P-gp protein in temporal cortex.Results:Compared with those of the sham operation group,the MRP_(1),P-gp mRNA content and protein expression in the hippocampus and temporal lobe cortex of the model group were significantly increased(P<0.01).Compared with those of the model group,the Pinggan Zhixian Compound combined with carbamazepine group could significantly reduce the MRP_(1),P-gp mRNA content and protein expression in the hippocampus and temporal lobe cortex areas(P<0.01,P<0.05).Compared with the carbamazepine group,the Pinggan Zhixian Compound combined with carbamazepine group had a better drug effect,and its effect was positively correlated with the level of administration dose.Conclusion:Pinggan Zhixian Compound combined with carbamazepine can significantly reduce the expression levels of MRP_(1) and P-gp in refractory epilepsy rats.Reversing and reducing the expression of MRP_(1) and P-gp protein in hippocampus may be one of the mechanisms of anti-drug-resistant epilepsy of the combination of P

关 键 词：平肝止痫复方 卡马西平 难治性癫痫大鼠 耐药性蛋白 

分 类 号：R285.5[医药卫生—中药学]