کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4303088 1288470 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Donor Pretreatment with DHMEQ Improves Islet Transplantation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Donor Pretreatment with DHMEQ Improves Islet Transplantation
چکیده انگلیسی

BackgroundCurrently, pancreatic islet transplantation to achieve normoglycemia in insulin-dependent diabetes mellitus (IDDM) requires two or more donors. This may be due to the inability to transplant functionally preserved and viable islets after isolation. Islets have already been subjected to various harmful stresses during the isolation process leading to apoptosis. One of the intracellular signaling pathways, the transcription factor nuclear factor-κB (NF-κB)-related pathway, is relevant to the mechanism of β-cell apoptosis in isolated islets. We attempted to prevent islet apoptosis during isolation by a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ).Materials and MethodsDHMEQ was injected intraperitoneally into donor mice 2 h prior to isolation. NF-κB activation, the functioning of isolated islets, apoptosis after isolation, and cytokine- and apoptosis-related genes were analyzed. After 160 equivalents of islets were transplanted into diabetic mice, graft survival and function were evaluated.ResultsIntra-islet NF-κB was activated immediately after isolation, and DHMEQ inhibited NF-κB activation without deterioration of islet function. DHMEQ significantly prevented apoptosis by inhibiting caspase 3/7 activities and down-regulated Bax, a pro-apoptotic gene. Donor pretreatment with DHMEQ significantly improved engraftment in syngeneic islet transplantation in mice, thus preserving insulin contents in the graft liver, as assessed by functional and histologic analyses.ConclusionsDHMEQ is a promising agent in islet transplantation because it protects islets from apoptosis during isolation stress. Donor pretreatment with DHMEQ can significantly affect the success of islet engraftment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 163, Issue 1, September 2010, Pages e23–e34
نویسندگان
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