The impact of acute rejection on the development of intimal hyperplasia associated with chronic rejection.
The impact of acute rejection on the development of intimal hyperplasia associated with chronic rejection.
复制标题
急性排斥反应对与慢性排斥反应相关的内膜增生发展的影响。
DOI：
10.1097/00007890-199612270-00028
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发表时间：
1996
期刊：
影响因子：
6.2
通讯作者：
Sollinger,HW
中科院分区：
文献类型：
--
作者：
Hullett,DA;Geraghty,JG;Stoltenberg,RL;Sollinger,HW
采用大鼠主动脉慢性排斥模型，研究急性排斥反应对内膜增生（IH）发生的影响。研究了两个模型系统。首先，移植后2或4周开始使用霉酚酸酯（MM）持续单药治疗（40 mg/d× 14 d，然后是30 mg/kg/d）。采用数字计算机图像分析定量IH。虽然推迟了IH的发展，但它并没有被阻止。在同种异体移植物中，MM治疗延迟2周，观察到IH量减少35.5%。延迟药物治疗4周导致IH降低42.2%。相比之下，与未治疗的同种异体移植对照相比，从移植开始持续治疗导致IH数量减少76.3%。为了进一步明确急性排斥反应在IH发生中的作用，我们将同种异体主动脉移植ACI或（acxi Lewis） f1 （f1）原位移植到Lewis受体，然后在2或4周后再移植到供体株继发受体中。移植后12周收获移植物。再移植2周时，与常规（ACI→Lewis）同种异体对照相比，ACI组内膜增生减少55.9%，f1组内膜增生减少66.7%。当再次移植延迟至4周时，ACI同种异体移植物的IH未降低（105.9%），f1同种异体移植物仅略微降低（26.2%）。同基因对照f1移植物（f1→f1→f1）在第2周再移植（分别为10%和12%）或第4周再移植并在第12周收获（18.6%）时，在12周或20周没有发生显著的IH。IH的一个共同特征是内侧脱细胞的发展。与传统的同种异体移植物受体（ACI→Lewis；无再移植）不同，f1再移植移植物未发生明显的内侧肌细胞脱落。相比之下，延迟MM免疫抑制治疗或在4周时再次移植ACI同种异体移植物给ACI继发受体会导致内侧肌细胞的显著损失。我们的研究结果表明，发生在移植后4周内的急性排斥反应足以介导与CR相关的IH的发展。然而，缺乏持续的同种异体环境会减缓这一过程。
The rat aortic model of chronic rejection was used to study the effect of acute rejection on the development of intimal hyperplasia (IH). Two model systems were studied. In the first, continuous monotherapy with mycophenolate mofetil (MM)(40 mg/d× 14 d followed by 30 mg/kg/d) was initiated 2 or 4 weeks posttransplant. Digital computer image analysis was used to quantify IH. While the development of IH was delayed, it was not prevented. In allografts where MM treatment was delayed for 2 wk, a 35.5% reduction in the amount of IH was observed. Delaying drug treatment for 4 wk resulted in a 42.2% reduction of IH. In contrast, continuous therapy from the time of transplant resulted in a 76.3% reduction in the amount of IH in comparison with untreated allograft controls. To further define the role of acute rejection in the development of IH, aortic allografts, ACI or (ACI× Lewis) F 1 (F 1), were orthotopically transplanted to Lewis recipients and then retransplanted to donor strain secondary recipients after 2 or 4 wk. Grafts were harvested at 12 weeks posttransplant. When the retransplant was performed at 2 wk, intimal hyperplasia was decreased by 55.9% in ACI and by 66.7% in F 1 allografts in comparison to conventional (ACI→ Lewis) allograft controls. When retransplantation was delayed until 4 wk, IH was not decreased in ACI allografts (105.9%) and was only marginally decreased in F 1 allografts (26.2%). Syngeneic control F 1 grafts (F 1→ F 1→ F 1) did not develop significant IH at 12 or 20 wk when retransplanted at 2 wk (10% and 12%, respectively) or when retransplanted at 4 wk and harvested at 12 wk (18.6%). A common feature of IH is the development of medial acellularity. Unlike conventional allograft recipients (ACI→ Lewis; no retransplantation), F 1 retransplanted grafts did not develop significant medial myocyte dropout. In contrast, delayed MM immunosuppressive therapy or retransplantation of ACI allografts at 4 weeks to ACI secondary recipients resulted in significant loss of medial myocytes. Our results show that acute rejection, which occurs during the first 4 wk posttransplant, is sufficient to mediate the development of IH associated with CR. However the lack of a continued allogenic environment slows the process.