Prevention of primary non-function of islet xenografts in autoimmune diabetic NOD mice by anti-inflammatory agents
Prevention of primary non-function of islet xenografts in autoimmune diabetic NOD mice by anti-inflammatory agents
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DOI：
10.1007/s00125-003-1154-0
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发表时间：
2003-08-01
期刊：
影响因子：
8.2
通讯作者：
Mathieu, C
中科院分区：
文献类型：
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作者：
Gysemans, C;Stoffels, K;Mathieu, C
目的/假说。移植后最初几天移植物局部高水平炎症可导致NOD小鼠移植物异种胰岛原发性无功能（PNF）。本研究旨在探讨抗炎药在自发性糖尿病NOD小鼠模型中预防异种胰岛移植后PNF的作用。将300个大鼠胰岛移植给自发性糖尿病NOD小鼠。动物分别用乙酰水杨酸（AsA）、罗非昔布、tgf - β或IL-1受体拮抗剂（IL-1ra）治疗。移植后8小时用实时PCR检测移植物内炎症相关分子的表达。在同一时间点，测定血浆亚硝酸盐水平。异种胰岛移植到对照组自发性糖尿病小鼠中，38只小鼠中有16只（42%）出现PNF。给予罗非昔布（30%）或tgf - β(25%)未改变初始移植物损失。AsA将移植物快速损失率降低至8% (p
Aims/hypothesis. High levels of inflammation locally in the graft during the initial days after transplantation can cause primary non-function (PNF) of grafted xenogeneic islets in NOD mice. The aim of this study was to explore in a model of spontaneous diabetes, the NOD mouse, the potential of anti-inflammatory agents in the prevention of PNF after xenogeneic islet transplantation.Methods. Spontaneously diabetic NOD mice were transplanted with 300 rat islets. Animals were treated with acetylsalicylic acid (AsA), rofecoxib, TGF-beta or IL-1 receptor antagonist (IL-1ra). Intra-graft expression of inflammation-related molecules was measured by real time PCR 8 h post-transplantation. At the same time point, plasma nitrite levels were measured.Results. Xenogeneic islets transplanted in control spontaneously diabetic mice resulted in PNF in 16 out of 38 mice (42%). Initial graft loss was not altered by administration of rofecoxib (30%) or TGF-beta (25%). AsA reduced the rate of rapid graft loss to 8% (p