FK506对糖尿病小鼠胰岛移植物功能及再血管化的影响

Effects of FK506 on function and revascularization of islet grafts in diabetic mice

目的探讨小鼠胰岛移植术后服用他克莫司（FK506）对胰岛移植物生物学功能及再血管化的影响。方法小鼠胰腺经胶原酶P灌注消化后，Ficoll．400不连续密度梯度离心提纯并培养制备供体胰岛。1型糖尿病受体小鼠接受肾被膜下胰岛移植并分成两组：单纯同系基因胰岛移植组（PIT组）和同系基因胰岛移植后加用FK506组（PIT＋FK506组）。监测受体小鼠血糖浓度的变化，观察移植物组织学形态、胰岛素分泌功能及新生血管生成情况。结果两组小鼠各时间点血糖浓度的变化差异无统计学意义（P〉0．05）。组织形态学观察发现两组小鼠胰岛移植物均存活良好，无明显差别。移植后第3～5天和第20天，PIT＋FK506组移植物血管内皮生长因子（VEGF）和CD34表达均较PIT组有所降低；PIT组肾被膜下移植物微血管密度分别为16．6±1．3和96．7±2．3，PIT＋FK506组分别为9．3±1．0和61．0±2．7，相同时间点两组间比较差异有统计学意义（P〈0．05）。结论治疗剂量的FK506可在一定程度上抑制胰岛移植物的再血管化，但不会直接影响胰岛细胞的生物学功能。

Objective To： investigate effects of FK506 on function and revascularization of transplanted islets after pancreatic islet transplantation （PIT） in diabetic mice. Methods Pancreatic islets of donor mice were obtained by infusion of eollagenase P solution with pancreatic duct and Ficoll-400 density gradient eentrifugation, then transplanted into renal capsule of type 1 diabetic mice. The recipients were divided into two groups： control group （PIT group） and FK506- treated group （ PIT ＋ FK506 group）. The blood glucose of recipients mice after islet transplantation were monitored. The histological feature, function of insulin secretion, and revascularization of the grafts were observed. Results The blood glucose on each time point had no significant differences between PIT group and PIT ＋ FK506 group （ P 〉 0.05）. Histological examination showed that all the islet grafts survived well and had no difference. On day 3 -5 and 20 after PIT, compared to PIT group, VEGF and CD34 expressions were significantly lower in PIT ＋ FK506 group. On day 3 - 5 and 20 after PIT, the newly-formed microvascular density of renal subcapsular islet grafts post transplantation !n PIT ＋ FK506 group （9.3±1.0 and 61.0±2.7） were significantly lower than those in PIT group （16.6± 1.3 and 96.7±2.3）（P 〈0.05）. Conclusion The therapeutic dose of FK506 inhibits the revascularization of transplanted pancreatic islets, but does not affect the insulin secretion of the transplanted grafts directly.