Sakr M, Zetti G, McClain C, Gavaler J, Nalesnik M, Todo S, Starzl T, Van Thiel D
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Transplantation. 1992 May;53(5):987-91. doi: 10.1097/00007890-199205000-00004.
The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr prior to the induction of renal ischemia. A 60-min period of ischemia of the right kidney was induced, and upon reperfusion a left nephrectomy was performed. Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats were sacrificed after day 10 and renal tissue was examined histologically. All animals survived the ischemic episode. FK506 pretreatment significantly reduced the serum levels of BUN (P less than 0.02), creatinine (P less than 0.02), and TNF (P less than 0.05) as compared with that seen in controls. Histologically, at day 10, the kidneys showed the expected sequelae of prior renal I/R with various degrees of tubular damage. However, no objective differences were evident between the two groups. Based upon these data, it can be concluded that (1) FK506 pretreatment ameliorates the functional renal injury associated with I/R, (2) renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in a significant inhibition of TNF production. These data suggest that the release of TNF may be responsible for the increasing of BUN and creatinine levels seen after renal I/R and that pretreatment of renal donors with FK506 may improve renal function in the immediate post-transplant period.
采用大鼠模型研究了FK506预处理对肾缺血再灌注（I/R）损伤的影响。将动物分为两组（每组20只大鼠）。第1组动物（对照组）接受0.5 ml生理盐水，而第2组动物接受FK506（0.3 mg/kg），在诱导肾缺血前24小时静脉注射。诱导右肾缺血60分钟，再灌注后行左肾切除术。在第0天（缺血前）、第1、2、3、5、7和10天（缺血后）采集血样，用于评估血尿素氮、肌酐和肿瘤坏死因子。10天后处死大鼠，对肾组织进行组织学检查。所有动物均在缺血期存活。与对照组相比，FK506预处理显著降低了血尿素氮（P<0.02）、肌酐（P<0.02）和肿瘤坏死因子（P<0.05）的血清水平。组织学上，在第10天，肾脏显示出先前肾I/R的预期后遗症，伴有不同程度的肾小管损伤。然而，两组之间没有明显的客观差异。基于这些数据，可以得出以下结论：（1）FK506预处理可改善与I/R相关的功能性肾损伤；（2）肾缺血诱导肿瘤坏死因子的释放；（3）FK506预处理可显著抑制肿瘤坏死因子的产生。这些数据表明，肿瘤坏死因子的释放可能是肾I/R后血尿素氮和肌酐水平升高的原因，并且用FK506预处理肾供体可能会改善移植后即刻的肾功能。
