Caillard S
Service de Néphrologie Transplantation, Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital, Strasbourg, France.
Nephrol Ther. 2009 Dec;5 Suppl 6:S379-84. doi: 10.1016/S1769-7255(09)73429-7.
Proliferation Signal inhibitors (PSI), sirolimus and everolimus, possess immunosuppressive and antiproliferative properties that have a substantial impact in organ transplantation. Their antiproliferative and pro-apoptotic action on vascular smooth muscle cells and endothelial cells, with positive effects on vascular remodeling, intimal proliferation, and atheroma plaques, has been demonstrated in many experimental studies in cell culture and on animal vascular, cardiac, and renal models. In humans, the PSI show a major advantage in heart transplantation, since they contribute satisfactory immunosuppression while preventing coronary vasculopathy related to intimal proliferation of smooth muscle cells, a factor that limits the long-term success of the graft. Intravascular ultrasound explorations, which measure intima thickness, showed that PIS treatment can inhibit intracoronary intimal proliferation after heart transplantation and thus reduce the morbidity and mortality at the medium term in transplantation patients. In kidney transplantation, even though their impact is less clear for the moment because of the multifactorial aspect of chronic graft dysfunction, the PSI nevertheless contribute undeniable benefits in terms of improving renal function and reducing the histological lesions of chronic allograft nephropathy.
增殖信号抑制剂(PSI),西罗莫司和依维莫司,具有免疫抑制和抗增殖特性,对器官移植有重大影响。它们对血管平滑肌细胞和内皮细胞的抗增殖和促凋亡作用,对血管重塑、内膜增殖和动脉粥样斑块有积极影响,这已在细胞培养以及动物血管、心脏和肾脏模型的许多实验研究中得到证实。在人类中,PSI在心脏移植中显示出主要优势,因为它们在预防与平滑肌细胞内膜增殖相关的冠状动脉血管病变(这是限制移植物长期成功的一个因素)的同时,能提供令人满意的免疫抑制。测量内膜厚度的血管内超声检查表明,PSI治疗可抑制心脏移植后冠状动脉内的内膜增殖,从而降低移植患者中期的发病率和死亡率。在肾脏移植中,尽管由于慢性移植功能障碍的多因素性质,目前它们的影响尚不太明确,但PSI在改善肾功能和减少慢性同种异体移植肾病的组织学病变方面仍有不可否认的益处。