从血脑屏障药物转运机制探究平痫冲剂的抗痫作用  

Exploration of the Anti Epileptic Effect of Pingxian Granules from the Perspective of Blood-Brain Barrier Drug Transport Mechanism

作　　者：高旅 王梓安 高蕾 尚菁 林蓉 史正刚 隋峰[2] GAO Lyu;WANG Zi'an;GAO Lei;SHANG Jing;LIN Rong;SHI Zhenggang;SUI Feng(Third College of Clinical Medicine,Shanxi University of Chinese Medicine,Taiyuan 030619,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Clinical College of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]山西中医药大学第三临床学院,太原030619 [2]中国中医科学院中药研究所,北京100700 [3]甘肃中医药大学中医临床学院,兰州730000

出　　处：《中国中医基础医学杂志》2024年第8期1362-1366,共5页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(82305318);山西省应用基础研究计划面上青年基金项目(201901D211536)。

摘　　要：目的观察平痫冲剂的抗痫作用,并探讨其作用机制。方法将62只3周龄Wistar大鼠随机分为空白组12只,造模组50只,采用戊四唑(pentetrazol,PTZ)腹腔注射制备癫痫模型;模型制备成功后,随机分成模型组、西药组及平痫冲剂组,每组各12只,西药组给予丙戊酸钠灌胃,平痫冲剂组给予平痫冲剂灌胃。干预7 d后,观察癫痫大鼠运动皮质区的组织形态结构;免疫组化、RT-qPCR以及Western blot检测大脑运动皮质区组织L型氨基酸转运体(L-type amino acid transporter,LAT)1、P糖蛋白(P-glycoprotein,P-gp)、乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)的表达情况。结果与空白组比较,模型组大鼠大脑运动皮质区神经元数量减少(P<0.01),LAT1蛋白及mRNA表达下降(P<0.05),P-gp、BCRP及其mRNA表达升高(P<0.05)。与模型组比较,平痫冲剂组大鼠大脑运动皮质区神经元数量增多(P<0.05),神经元病理形态有所改善,LAT1及其mRNA表达升高(P<0.01),P-gp、BCRP及其mRNA表达下降(P<0.01)。结论平痫冲剂可能通过调控血脑屏障(blood-brain barrier,BBB)药物转运体P-gp、BCRP、LAT1的表达,从而发挥抗痫作用。Objective Observe the anti-epileptic effect of Pingxian granule and explore its mechanism.Methods 62 Wistar rats aged 3 weeks were randomly divided into two groups:a control group with 12 rats and a model group with 50 rats.The Pentetrazol(PTZ)intraperitoneal injection was used to induce the epilepsy model.After the successful preparation,the model rats were randomly divided into a model group,a western medicine group,and a Pingxian granule group,with 12 rats in each group.The western medicine group was administered with sodium valproate by gavage,the Pingxian granule group was administered with Pingxian granule by gavage.After 7 days of intervention,the morphological structure of the motor cortex in epileptic rats was observed.Immunohistochemistry,RT-qPCR,and Western blot were used to detect the expression of L-type amino acid transporter(LAT)1,P-glycoprotein(P-gp),and breast cancer resistance protein(BCRP)in the motor cortex tissue of the brain.Results The number of neurons in the motor cortex,and the expression of LAT1 protein and mRNA decreased(P<0.05),while the expression of P-gp,BCRP and their mRNA increased(P<0.05)for the model group rats,compared with the control group.Furthermore,the number of neurons in the motor cortex of rats in the Pingxian granule group increased(P<0.05),and the pathological morphology of neurons was improved.LAT1 and its mRNA expression were upregulated(P<0.01),while P-gp,BCRP,and their mRNA expression were downregulated(P<0.01),compared with the model group.Conclusion Pingxian granule may exert its anti-epileptic effect by regulating the expression of blood-brain barrier(BBB)drug transporters P-gp,BCRP and LAT1.

关 键 词：癫痫 平痫冲剂 血脑屏障 药物转运机制 L型氨基酸转运体1 P糖蛋白 乳腺癌耐药蛋白 

分 类 号：R272.6[医药卫生—中医儿科学]