Experimental study of FR167653 in simultaneous pancreas and kidney transplantation from non-heart-beating donor

FR167653在无心跳供体同步胰肾移植中的实验研究

• 批准号: 14571142
• 负责人: SUGITANI Atushi
• 金额: $ 2.24万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571142/
• 关键词: pancreas transplantation; kidney transplantation; warm ischemia; ischemia-reperfusion; FR167653; cytokine; 虚血再潅流障害; 温疎血; 蛋白分解酵素阻害剤; アポトーシス

Background. Inflammatory cytokines are known to contribute to ischemia-reperfusion (LIR) injury. We investigated the effect of FR167653 (FR), a suppressor of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, on I/R injury of the kidney in dogs.Methods. The left kidney was subjected to ischemia for 60 minutes followed by removal of the right kidney. A control group (n=10) and an FR group (n=8) were evaluated for tissue blood flow ; resistive_index, pulsatilitv_index arterial oxygen pressure (PaO_2), serum creatinine, blood urea nitrogen (BUN), aspartate transaminase (AST), and alanine transaminase (ALT) levels ; IL-1β mRNA expression in the peripheral blood ; apoptotic index ; and histopathology.Results. The FR group showed lower creatinine, BUN, AST, and ALT levels (p<0.038 each) : and lower IL-1β mRNA expression and apoptotic index (p<0.041 each) than did the control group. PaO_2 during 120 minutes after reperfusion in the FR group dropped but recovered quickly (p=0.024). Renal tissue damage in the FR group was less than that in the control group (p=0.036).Conclusions. FR ameliorates I/R injury of the kidney potentially via reduced production of inflammatory cytokines that may contribute to damage to the ischeniic kidney and the distant organs.

背景。已知炎症细胞因子有助于缺血再灌注（LIR）损伤。我们研究了白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的抑制因子FR167653 （FR）对狗肾I/R损伤的影响。左肾缺血60分钟后取出右肾。对照组（n=10）和FR组（n=8）评估组织血流量；电阻指数、脉搏指数、动脉血氧压（PaO_2）、血肌酐、血尿素氮（BUN）、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）水平；外周血IL-1β mRNA表达；凋亡指数；和histopathology.Results。FR组肌酐、BUN、AST、ALT水平均低于对照组（p<0.038）， IL-1β mRNA表达和凋亡指数均低于对照组（p<0.041）。FR组再灌注120 min时PaO_2下降，但恢复较快（p=0.024）。FR组肾组织损伤明显小于对照组（p=0.036）。FR可能通过减少炎症细胞因子的产生来改善肾I/R损伤，炎症细胞因子可能导致缺血肾和远端器官受损。