Räisänen-Sokolowski A, Aho P, Tufveson G, Häyry P
Transplantation Laboratory, University of Helsinki, Finland.
Transpl Int. 1994;7 Suppl 1:S376-7. doi: 10.1111/j.1432-2277.1994.tb01395.x.
Chronic rejection is a major cause for late graft loss. Typical vascular changes in the grafts are adventitial inflammation, disappearance of myocytes in the media and thickening of the intimal layer. We investigated the effect of a new immunosuppressive drug, 15-deoxyspergualin (DSG), on chronic rejection using our rat aortic allograft model. At the dose of 1.0 mg/kg per day, DSG significantly reduced all histopathological parameters of chronic rejection, thus, inhibiting the generation of allograft arteriosclerosis. Growth factor synthesis in the grafts was determined by reverse transcription reaction with oligo dT primers and semiquantitated by polymerase chain reaction. The expression of several growth factors, PDGF-BB, IGF-1, EGF an TGF-beta, was suppressed to 16-60% of the non-treated allograft level. This indicated that DSG may work via suppression of growth factor synthesis and, thus, inhibits the generation of chronic rejection.
慢性排斥反应是移植器官晚期丧失功能的主要原因。移植器官典型的血管变化是外膜炎症、中膜肌细胞消失和内膜层增厚。我们使用大鼠主动脉同种异体移植模型，研究了一种新型免疫抑制药物15-脱氧精胍菌素（DSG）对慢性排斥反应的影响。每天剂量为1.0mg/kg时，DSG显著降低了慢性排斥反应的所有组织病理学参数，从而抑制了同种异体移植动脉硬化的发生。通过用oligo dT引物进行逆转录反应来测定移植器官中的生长因子合成，并通过聚合酶链反应进行半定量。几种生长因子PDGF-BB、IGF-1、EGF和TGF-β的表达被抑制至未处理的同种异体移植水平的16%-60%。这表明DSG可能通过抑制生长因子合成起作用，从而抑制慢性排斥反应的发生。
