FTY720在鼠类异种胰岛移植排斥反应中的作用

目的 在小鼠异种胰岛细胞移植模型上，研究FTY720在控制异种胰岛移植排斥反应中的作用。方法 使用胰管内胶原酶注射和不连续密度梯度纯化法获取大鼠胰岛，建立小鼠肾被膜下移植模型。受体小鼠随机分为3组：对照组，末使用任何免疫抑制药物；实验1组，自移植当日起每日单独喂服FTY720(1.0mg／kg)；实验2组，亦于移植当日起每日联合喂服FTY720(1.0mg／kg)和环孢霉素A(CsA，15mg／kg)，均连续喂饲14d。分别于术后第3，5，7，14天切取移植物，观察并分析排斥反应。结果 对照组和实验1组，植入。肾被膜下的胰岛组织多在1周内完全被排斥，术后第7天胰岛轮廓消失，仅见大量淋巴细胞浸润。实验2组于移植后第7天及第14天肾被膜下仍可见大量完整的胰岛细胞，几乎未见或偶尔可见淋巴细咆浸润。结论 FTY720单独作为免疫抑制剂并不能抑制鼠类异种胰岛移植的排斥反应；联合应用FTY720及CsA则可有效地抑制鼠类异种胰岛移植排斥反应的发生。

Effect of FTY720 on pancreas islet xenograft rejection

Objective To evaluate the effect of FTY720 on pancreas islet xenograft rejection by setting up the rat-to-mouse islet xenotransplantation model. Methods Rat islets were harvesed by means of pancreatic duct irregution with collagenase and purified by discontinuous density gradient method. Then the islets were transplanted under the kidney capsule of the mouse. The recipients were divided into 3 groups randomly: control group,the mouth was administrated with saline without any immunosuppressant; experiment group 1,the mouth was administrated with FTY720 (1.0 mg/kg) orally from the operation day to day 14 after operation; experiment group 2,the mouth was administrated with combination of FTY720(1.0 mg/kg) with CsA(15 mg/kg) from the operation day to day14 after operation. The xenograft were removed with the kidney at day 3, 5, 7 and 14 after transplantation, and the rejection was analyzed. Results In the control group and experiment group 1, the xenografts were completely destroyed within one week; on day 7, no intact islets could be seen, but numerous lymphocytes infiltration were found. In experiment group 2, many intact islets were still seen under the kidney capsule in day7 and 14 after operation; and infiltrated lymphocytes could hardly or just occasionally be found. Conclusions FTY720 alone can not inhibit the rejection of islet xenotransplantation; FTY720 combination with CsA can inhibited islet xenograft rejection effectively in the rat-to-mouse model.