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

背景已知炎性细胞因子有助于缺血再灌注（LIR）损伤。本研究观察了白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α抑制剂FR 167653（FR）对犬肾I/R损伤的影响。使左肾缺血60分钟，然后切除右肾。评价对照组（n=10）和FR组（n=8）的组织血流量;阻力指数、脉动指数动脉血氧分压（PaO_2）、血清肌酐、血尿素氮（BUN）、天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平;外周血中IL-1β mRNA表达;细胞凋亡指数;和组织病理学。结果。与对照组相比，FR组显示出较低的肌酐、BUN、AST和ALT水平（均p<0.038），以及较低的IL-1β mRNA表达和凋亡指数（均p<0.041）。再灌注后120分钟内，FR组PaO_2下降，但很快恢复（p=0.024）。FR组的肾组织损伤小于对照组（p=0.036）。FR可能通过减少可能导致缺血肾和远端器官损伤的炎性细胞因子的产生来改善肾的I/R损伤。

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.