Kneteman N M, Rajotte R V, Procyshyn A W
J Surg Res. 1985 Oct;39(4):285-93. doi: 10.1016/0022-4804(85)90104-0.
Allograft rejection is the major obstacle to clinical pancreatic islet transplantation. We attempted Cyclosporine A (CsA) immunosuppression of intrasplenic pancreatic dispersed fragment allografts in unrelated, unmatched dogs. Animals underwent (1) pancreatectomy only, (2) autotransplantation, or allotransplantation with (3) no immunosuppression (NIL), (4) azathioprine (AZA 3 mg/kg/day) and prednisone (PRED 2 mg/kg/day), or (5) CsA (25 mg/kg/day). Graft preparation was by collagenase ductal perfusion and mechanical disruption and transplantation was by splenic venous reflux. Rejection was defined by permanent hyperglycemia (greater than 150 mg/dl). Apancreatic dogs survived 6.0 +/- 0.5 days; autotransplanted dogs remained normoglycemic at 6 months. Rejection occurred at NIL, 5.0 +/- 0.6 days; AZA/PRED, 1.8 +/- 0.3 days; and CsA, 19.3 +/- 5.6 days. Survival was NIL, 16.0 +/- 3.4 days; AZA/PRED, 13.4 +/- 1.4 days; and CsA, 33.3 +/- 4.6 days. CsA showed significant advantage over both groups in both time to rejection (P less than 0.05) and survival (P less than 0.01). CsA toxicity was minimal. CsA achieved significant delay in rejection and improved survival in unmatched, unrelated dogs after intrasplenic allotransplantation with pancreatic dispersed fragments.
同种异体移植排斥是临床胰岛移植的主要障碍。我们尝试用环孢素A（CsA）对不相关、不匹配犬的脾内胰腺分散碎片同种异体移植进行免疫抑制。动物接受（1）仅胰腺切除术，（2）自体移植，或同种异体移植，其中（3）不进行免疫抑制（无免疫抑制组），（4）硫唑嘌呤（AZA 3毫克/千克/天）和泼尼松（PRED 2毫克/千克/天），或（5）CsA（25毫克/千克/天）。移植物制备采用胶原酶导管灌注和机械破碎，移植采用脾静脉回流。排斥反应定义为持续性高血糖（大于150毫克/分升）。胰腺切除的犬存活6.0±0.5天；自体移植的犬在6个月时仍保持血糖正常。无免疫抑制组在5.0±0.6天发生排斥反应；AZA/PRED组在1.8±0.3天发生；CsA组在19.3±5.6天发生。无免疫抑制组的存活时间为16.0±3.4天；AZA/PRED组为13.4±1.4天；CsA组为33.3±4.6天。CsA在排斥反应时间（P<0.05）和存活时间（P<0.01）方面均显示出优于两组的显著优势。CsA的毒性最小。在不相关、不匹配犬进行脾内胰腺分散碎片同种异体移植后，CsA显著延迟了排斥反应并提高了存活率。
