Ericzon B G, Wijnen R M, Tiebosch A, Kubota K, Kootstra G, Groth C G
Department of Transplantation Surgery, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Transplantation. 1992 Jun;53(6):1184-9. doi: 10.1097/00007890-199206000-00003.
The effect of FK506 monotherapy on pancreaticoduodenal allotransplantation was studied in a primate model. The recipients were made diabetic by total pancreatectomy, thus glycemic control depended on the graft. In control animals hyperglycemia occurred after 14 +/- 3 days and the animals died after 36 +/- 15 days. For FK506-treated animals, the time until development of hyperglycemia was 60 +/- 12 days (P less than 0.05). The animals were then sacrificed by day 90 (P less than 0.05). All three control animals lost their graft function because of severe rejection, as verified by postmortem examination. Only one of the five treated animals showed evidence of a moderate-to-severe rejection at 90 days, one animal having a mild rejection as judged by the histological findings. The drug was clinically well tolerated in all except one animal that became apathetic and refused to eat. Hyperglycemia and an elevated serum creatinine level, which were probably related to the FK506 treatment, occurred in one animal each. Both of these side-effects were reversed by reducing the dose. Thus the use of FK506 permits successful single pancreatic transplantation in primates.
在灵长类动物模型中研究了FK506单一疗法对胰十二指肠同种异体移植的影响。通过全胰切除术使受体患糖尿病，因此血糖控制依赖于移植物。在对照动物中，14±3天后出现高血糖，动物在36±15天后死亡。对于接受FK506治疗的动物，出现高血糖的时间为60±12天（P<0.05）。然后在第90天时处死动物（P<0.05）。所有三只对照动物因严重排斥反应而失去移植物功能，尸检证实了这一点。五只接受治疗的动物中只有一只在90天时出现中度至重度排斥反应的迹象，根据组织学结果判断，有一只动物出现轻度排斥反应。除一只变得冷漠并拒绝进食的动物外，所有动物对该药物的临床耐受性良好。高血糖和血清肌酐水平升高分别出现在一只动物中，这可能与FK506治疗有关。通过降低剂量，这两种副作用均得到逆转。因此，使用FK506可使灵长类动物成功进行单一胰腺移植。
