Busauschina A, Schnuelle P, van der Woude F J
Vth Medical Clinic (Nephrology, Endocrinology), University Hospital Mannheim, Medical Faculty of the University of Heidelberg, Mannheim, Germany.
Transplant Proc. 2004 Mar;36(2 Suppl):229S-233S. doi: 10.1016/j.transproceed.2004.01.021.
Cyclosporine (CsA) is the current primary immunosuppressant for the prevention of allograft rejection in solid organ transplantation. However, owing to its molecular mechanism of action the drug is associated with various adverse side effects (eg, nephrotoxicity). Histological changes appear as obliterative vasculopathy of the afferent arteriole and tubulointerstitial fibrosis in advanced cases. The underlying pathomechanisms of this condition reflect an altered release of vasoactive substances, such as angiotensin II, endothelin, prostaglandins, and nitric oxide as well as the stimulation of proliferative genes such as transforming growth factor-beta, osteopontin, and collagen I and IV. Potential strategies for the prevention of nephrotoxicity are discussed.
环孢素(CsA)是目前实体器官移植中预防同种异体移植排斥反应的主要免疫抑制剂。然而,由于其作用的分子机制,该药物会引发各种不良副作用(如肾毒性)。在晚期病例中,组织学变化表现为入球小动脉的闭塞性血管病变和肾小管间质纤维化。这种情况的潜在病理机制反映了血管活性物质(如血管紧张素II、内皮素、前列腺素和一氧化氮)释放的改变,以及增殖基因(如转化生长因子-β、骨桥蛋白和I型及IV型胶原蛋白)的刺激。文中讨论了预防肾毒性的潜在策略。