首页|慢性肾脏病中肾脏药物转运体变化的研究进展

慢性肾脏病中肾脏药物转运体变化的研究进展

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慢性肾脏病(chronic kidney disease,CKD)是一种由各种原因导致的肾脏结构与功能逐渐丧失,病程超过3个月,临床表现为不同程度尿蛋白、浮肿、高血压、肾功能损伤等的一组综合征.药物转运体在肾脏中发挥着重要作用,与药物吸收、分布、代谢和排泄有关,这些药物转运体被认为是决定药物在细胞内积累的关键因素.CKD可以导致肾脏药物转运体的异常表达和功能障碍,从而影响药物及其代谢产物的清除和毒性.该文系统阐述肾脏药物转运体,包括溶质载体家族(solute carrier transporter,SLC)和ATP结合盒家族(ATP-binding cassette transporter ABC),在CKD状态下变化的研究进展,肾脏上P-糖蛋白(P-gp)、乳腺癌抗性蛋白(BCRP)、有机阴离子转运体1(OAT1)等转运体的表达下调,多药耐药相关蛋白2(MRP2)、有机阴离子转运多肽1A4(OATP1A4)、有机阴离子转运多肽1A5(OATP1A5)等转运体表达上调.今后需进一步阐明肾脏药物转运体在CKD下变化的作用机制以及其他器官在CKD状态下的调控情况,为寻找治疗CKD的新策略和临床合理用药提供理论和实践基础.
Research progress on the changes of renal drug transporters in chronic kidney disease
As a progressive condition characterized by a gradual loss of kidney structure and function,chronic kidney disease(CKD)generally lasts for more than 3 months.It presents as a syndrome with various clinical manifestations of proteinuria,edema,hypertension and renal impairment.Play a crucial role in kidney,drug transporters are involved in drug absorption,distri-bution,metabolism and excretion.These drug transporters are considered key factors in determining drug accumulation within cells.CKD may result in abnormal expression and functional impairment of renal drug transporters,thereby affecting the clearance and toxicity of drugs and their metabolites.This review focused upon some common renal drug transporters of solute carrier trans-porter(SLC)family and ATP-binding cassette transporter(ABC)and discussed the latest researches on their alterations under CKD conditions.It highlighted a down-regulation of such transporters as P-glycoprotein(P-gp),breast cancer resistance protein(BCRP)and organic anion transporter 1(OAT1)in kidney,as well as an up-regulation of such transporters as multidrug resis-tance protein 2(MRP2),organic anion-transporting polypeptide 1A4(OATP1A4)and organic anion-transporting polypeptide 1A5(OATP1A5).Further mechanistic elucidations of underlying changes in renal drug transporters in CKD,as well as regula-tory status of drug transporters in other organs under CKD conditions,is required for providing theoretical and practical rationales for formulating new strategies for treating CKD and promoting rational drug use in clinical practices.

chronic kidney diseaserenal drug transporterssolute carrier transporterATP-binding cassette transporterexpression/functional changes

叶梦晗、张蕊、刘亚妮、师少军

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华中科技大学同济医学院协和医院药学部,湖北武汉 420022

慢性肾脏病 肾脏药物转运体 溶质载体家族 ATP结合盒家族 表达/功能变化

国家自然科学基金面上项目国家自然科学基金面上项目国家自然科学基金面上项目

821739028210427481874326

2024

10.13286/j.1001-5213.2024.12.18

中国医院药学杂志
中国药学会

中国医院药学杂志

CSTPCD北大核心
影响因子：1.198
ISSN：1001-5213
年,卷(期)：2024.44(12)