他克莫司与肾小管毒性:机制与防治  

Tacrolimus and Renal Tubular Toxicity:Mechanism and Prevention

作　　者：胡帮环 苏华[1] Hu Banghuan;Su Hua(Department of Nephrology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院肾内科,武汉430022

出　　处：《华中科技大学学报(医学版)》2025年第1期117-122,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.82170773)。

摘　　要：他克莫司(tacrolimus,FK506)是应用最广泛的钙调神经磷酸酶抑制剂(calcineurin inhibitors,CNIs),也是免疫抑制治疗方案中的一线用药。FK506是一种治疗指数狭窄的药物,其个体间和个体内的药代动力学差异较大,长期或短期内高剂量暴露于FK506会导致肾毒性。肾脏中近端小管细胞是唯一能够代谢CNIs的细胞,近端小管细胞被认为在这类药物的毒性起源中起着核心作用。FK506诱导的肾小管毒性机制复杂,涉及细胞氧化应激、炎症反应、肾小管细胞代谢功能障碍、细胞凋亡以及肾素-血管紧张素系统等因素。尽管经过多年的研究,FK506诱导的肾小管毒性发病机制仍未完全阐明。基于此,该文旨在综述他克莫司相关肾小管毒性的发病机制及其防治的研究进展,以期为临床治疗和未来研究提供参考。Tacrolimus(FK506)is the most widely utilized calcineurin inhibitors(CNIs)and serves as the first-line agent in immunosuppressive treatment regimens.FK506 has a narrow therapeutic index,and its pharmacokinetics exhibit significant variability both between and within individuals.High-dose exposure to FK506,whether administered long-term or short-term,can result in nephrotoxicity.Proximal tubule cells in kidney are the only cells that are capable of metabolizing CNIs,and these cells are believed to play a central role in the development of toxicity associated with this class of drugs.The mechanism underlying renal tubular toxicity induced by FK506 is complex,involving factors such as cellular oxidative stress,inflammatory responses,metabolic dysfunction of renal tubular cells,apoptosis,and the renin-angiotensin system.Despite extensive research,the pathogenesis of FK506-induced tubular toxicity remains incompletely understood.Therefore,this article aims to review the research progress concerning the pathogenesis of tacrolimus-related renal tubular toxicity,as well as its prevention and treatment,to provide a reference for clinical practice and future research.

关 键 词：他克莫司 肾小管毒性 机制 防治药物 

分 类 号：R586[医药卫生—内分泌]