论文部分内容阅读
大环内酯类抗真菌抗生素雷帕霉素(RAPA)有强效免疫抑制和抗细胞增殖活性,国内外已广泛用于肾、心、肝等实体器官移植后急性排斥反应的防治,因无肾毒性而优于环孢素A。RAPA主要抑制细胞增殖、生存信号Ras/PI3k/Akt途径下游哺乳类雷帕霉素靶蛋白(mTOR),使细胞增殖周期停滞在G1期而凋亡,主要副作用为高脂血症。临床上已用于治疗骨髓增生异常综合征和急性白血病等。本文简述RAPA的药物动力学、毒副作用和作用机制,并指出RAPA用于防治造血干细胞移植后移植物抗宿主病(GVHD)、恶性血液病和免疫性疾病可能有较好的临床应用前景。
Macrolide antifungal antibiotics rapamycin (RAPA) has potent immunosuppressive and anti-cell proliferative activity, and has been widely used in prevention and treatment of acute rejection after solid organ transplantation such as kidney, heart and liver at home and abroad. Nephrotoxicity is superior to cyclosporin A. RAPA mainly inhibits cell proliferation and rapamycin target protein (mTOR) downstream of the Ras / PI3k / Akt pathway in survival signaling, which arrests the cell cycle and arrests in G1 phase. The main side effect is hyperlipidemia. Clinically used to treat myelodysplastic syndrome and acute leukemia. This article describes the pharmacokinetics, side effects and mechanism of RAPA, and points out that RAPA may have better clinical application prospects in the prevention and treatment of graft-versus-host disease (GVHD), hematologic malignancies and immune diseases after hematopoietic stem cell transplantation.