离子通道在骨关节炎发病机制中的作用研究进展

Research progress of ion channels in the pathogenesis of osteoarthritis

由于离子通道参与许多细胞过程,作用于离子通道的药物长期以来被用于治疗许多疾病,特别是那些影响组织细胞电兴奋的疾病。随着离子通道病理学机制的不断研究,离子通道已被确定为潜在的新药靶点,许多针对离子通道的基础药物的治疗价值得到了证实。对药物-离子通道相互作用的实验研究表明,离子通道突变可以增加或减少对药物的亲和力,改变其潜在的治疗效果。与可能影响药物药效的通道基因多态性的发现一样,这些发现强调了离子通道研究的必要性,以便识别对通道亚型或突变体有更具体作用的药物,以提高疗效和减少不良反应。随着对离子通道遗传学、结构和功能的更深入理解,以及对新一级和二级离子通道疾病的识别,用于骨关节炎(osteoarthritis,OA)的离子通道药物的数量将大幅增加。笔者就离子通道在OA发病机制中的作用进行了综述,重点介绍了电压门控钠通道Nav1.7、嘌呤类受体P2X3、瞬时感受器电位受体TRPV1、氯离子(Cl^(-))通道。从而进一步指导药物研发,以期为OA的诊疗和机制研究提供参考依据。

Because ion channels are involved in many cellular processes,drugs acting on ion channels have long been used to treat many diseases,especially those affecting the electrical excitation of tissue cells.With the continuous study of the pathological mechanism of ion channels,ion channels have been identified as potential new drug targets,and the therapeutic value of many basic drugs for ion channels has been confirmed.The experimental study of drug ion channel interaction shows that ion channel mutation increases or reduces the affinity for drugs and changes its potential therapeutic effect.Like the discovery of channel gene polymorphisms that may affect drug efficacy,these findings emphasize the necessity of ion channel research in order to identify drugs with more specific effects on channel subtypes or mutants in order to improve efficacy and reduce side effects.With a deeper understanding of ion channel genetics,structure and function,as well as the identification of new primary and secondary ion channel diseases,the number of ion channel drugs for the treatment osteoarthritis(OA)increases significantly.This paper reviews the role of ion channels in the pathogenesis of OA,focusing on voltage-gated sodium channel Nav1.7,purine receptor P2X3,transient receptor potential receptor TRPV1,and chloride(CL-)channel,in order to further guide drug research and development,and to provide reference basis for the diagnosis,treatment,and mechanism research of OA.