Rooth P, Dawidson I, Lafferty K, Diller K, Armstrong J, Pratt P, Simonsen R, Täljedal I B
Department of Surgery, University of Texas, Southwestern Medical Center, Dallas 75235.
Diabetes. 1989 Jan;38 Suppl 1:202-5. doi: 10.2337/diab.38.1.s202.
The revascularization of pancreatic islet clusters transplanted beneath the renal capsule was studied in a syngeneic mouse model. The degree of vascular ingrowth was visualized by in vivo fluorescence microscopy (fluorescein isothiocyanate-dextran) and judged by a semiquantitative method from coded video recordings. The recipients of isografts were divided into four groups, depending on their daily immunosuppressive treatment: 1) none (controls), 2) 15 mg/kg cyclosporin A (CsA), 3) 0.4 mg/kg verapamil + 15 mg/kg CsA, and 4) 20-30 mg/kg methylprednisolone. In control animals, capillary ingrowth was first demonstrated on day 6, followed by progressive vascularization up to day 34. After 6 mo, the vascular architecture was similar to that seen in normal islets in situ. CsA alone significantly decreased vascular ingrowth on day 14 compared with controls (P less than .02). Verapamil prevented the detrimental effect of CsA (P less than .01), probably by improving renal subcapsular blood flow. Methylprednisolone did not affect revascularization compared with control animals at day 14. We conclude that CsA inhibits vascular ingrowth into transplanted pancreatic islets, which is likely to have clinical implications. The prevention of CsA vascular ingrowth inhibition by a calcium antagonist indicates a possible approach to the correction of this problem, particularly when the renal capsule is used as the recipient's transplant site.
在同基因小鼠模型中研究了移植于肾被膜下的胰岛团簇的血管再生情况。通过体内荧光显微镜（异硫氰酸荧光素 - 葡聚糖）观察血管长入程度，并根据编码视频记录采用半定量方法进行判断。根据每日免疫抑制治疗情况，将同基因移植受体分为四组：1）无治疗（对照组），2）15mg/kg环孢素A（CsA），3）0.4mg/kg维拉帕米 + 15mg/kg CsA，4）20 - 30mg/kg甲泼尼龙。在对照动物中，第6天首次出现毛细血管长入，随后血管逐渐形成直至第34天。6个月后，血管结构与正常原位胰岛相似。与对照组相比，单独使用CsA在第14天时显著减少了血管长入（P <.02）。维拉帕米可预防CsA的有害作用（P <.01），可能是通过改善肾被膜下血流实现的。在第14天时，与对照动物相比，甲泼尼龙对血管再生没有影响。我们得出结论，CsA抑制血管长入移植的胰岛，这可能具有临床意义。钙拮抗剂预防CsA对血管长入的抑制作用表明了纠正这一问题的一种可能方法，特别是当肾被膜用作受体移植部位时。
