他克莫司致器官移植后新发糖尿病的发病机制研究进展

Research on Nosogenesis of New-onset Diabetes Mellitus After Transplantation Induced by Tacrolimus

器官移植术后新发糖尿病是实体器官移植后的主要并发症之一,免疫抑制常被认为是导致器官移植术后新发糖尿病的主要因素,包括糖皮质激素、钙调磷酸酶抑制剂等。其中,钙调磷酸酶抑制剂对血糖的影响最大。他克莫司是从链霉菌属中分离出的发酵产物,是一种强效免疫抑制性大环内酯类抗生素,现广泛用于实体器官移植的免疫抑制剂。他克莫司对细胞免疫有选择性抑制作用,主要通过抑制白细胞介素-2的释放,全面抑制T淋巴细胞的作用。通过查阅文献,从三方面综述了他克莫司引起高血糖的机制,包括影响β细胞存活和复制、影响胰岛素分泌、影响外周组织的胰岛素利用。

New-onset diabetes mellitus （NODM） after organ transplantation is one of the major complications after solid organ transplantation. Immunosuppression is considered as the main factor leading to NODM after organ transplantation, the immunosuppressive agents include glucocorticoids and calcineurin inhibitors, etc. and calcineurin inhibitors have a big effect on blood sugar. Tacrolimus is the fermented products isolated from Streptomyces, it is a macrolide antibiotic with potent immunosuppression and is now widely used as an immune inhibitor in organ transplants. Tacrolimus has a selective inhibitory action on cellular immunity, primarily by inhibiting the release of leukotriene -2 to inhibit the role of T lymphocytes. Based on the research of foreign literatures, this paper respectively discussed from three aspects of mechanism of hyperglycemia induced by tacrolimus, including the effects on β-cell survival and replication, insulin secretion and the influence of peripheral tissue insulin action.