雷帕霉素及其衍生物治疗局灶节段性肾小球硬化

Progress in application of mTORC1 inhibitors in focal segmental glomerulosclerosis

局灶节段性肾小球硬化(FSGS)治疗药物有限,亟待探讨新的治疗药物。近年研究证实,哺乳动物雷帕霉素靶蛋白复合物1(mTORC1)过度活化介导足细胞损伤和FSGS发病机制。mTORC1抑制剂雷帕霉素及其衍生物理论上可抑制足细胞过度活化的mTORC1,从而保护足细胞,目前已被用于FSGS患者的临床试验,然而其在部分患者显现的肾脏不良反应限制了此药的进一步应用。本文对雷帕霉素及其衍生物用于FSGS治疗的相关研究进展加以综述。

Drugs used for focal segmental glomerulosclerosis(FSGS)are limited.It is in need to explore new drugs.Hyperactivation of mammalian target of rapamycin complex 1(mTORC1)in podocyte has been confirmed to be an important pathway leading to podocyte injury of FSGS.mTORC1 inhibitors such as rapamycin can alleviate FSGS lesions by inhibiting hyperactivation of mTORC1 in podocyte theoretically and have been used in clinical trials of patients with FSGS.However,the nephrotoxicity in some patients limits its further use.The progress in studies on mTORC1 inhibitors in FSGS is reviewed in this article.