Improvement of canine islet yield by donor pancreas infusion with a p38MAPK inhibitor
Improvement of canine islet yield by donor pancreas infusion with a p38MAPK inhibitor
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DOI：
10.1097/tp.0b013e31817ef6c9
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发表时间：
2008-07-27
期刊：
影响因子：
6.2
通讯作者：
Mullen, Yoko
中科院分区：
文献类型：
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作者：
Ito, Tathei;Omori, Keiko;Mullen, Yoko
背景p38丝裂原活化蛋白激酶（MAPK）的激活参与了供体器官冷缺血再灌注损伤。从胰腺获取到胰岛收集的胰岛分离过程可能激活p38 MAPK，导致细胞因子释放和胰岛损伤。这种损伤可以通过在冷冻前用p38 MAPK抑制剂（p381 H）治疗胰腺来预防。将从比格犬中取出的胰腺通过胰管输注含有p38 IH、SB 203580和Pefabloc的威斯康星州大学溶液（n=6）或单独的溶剂（二甲基亚砜和Pefabloc）（n=7），并使用双层方法保存。20 ~ 22 h后，分离胰岛，将3000 IEQ/kg的胰岛自体移植到相应的犬体内，以监测葡萄糖代谢。p38 IH处理的胰腺产生的胰岛显著多于对照胰腺（IEQ/g：2134 +/- 297 vs. 1477 +/- 145 IEQ/g或65，012 +/- 9385 vs. 45，700 +/- 5103 IEQ/胰腺; P
Background. The activation of p38 mitogen-activated protein kinases (MAPK) is implicated in cold ischemia-reperfusion injury of donor organs. The islet isolation process, from pancreas procurement through islet collection, may activate p38MAPK leading to cytokine release and islet damage. This damage may be prevented by treating pancreata with a p38MAPK inhibitor (p381H) before cold preservation.Methods. Pancreata removed from Beagle dogs were infused with University of Wisconsin solution containing the p38IH, SB203580, and Pefabloc (n=6) or vehicle (dimethyl sulfoxide and Pefabloc) alone (n=7), through the pancreatic duct and preserved using the two-layer method. After 20 to 22 hr, islets were isolated and 3000 IEQ/kg were autotransplanted into the corresponding dog to monitor glucose metabolism.Results. p38IH-treated pancreata yielded significantly more islets than control pancreata (IEQ/g: 2134 +/- 297 vs. 1477 +/- 145 IEQ/g or 65,012 +/- 9385 vs. 45,700 +/- 5103 IEQ/pancreas; P