Cacciarelli T V, Sumrani N B, Hong J H, Chen C K, Sommer B G
Department of Surgery, State University of New York Health Science Center at Brooklyn.
ASAIO J. 1994 Oct-Dec;40(4):964-7.
The influence of timing of FK 506 (Tacrolimus) administration on renal function and recovery from renal warm ischemia was studied in Sprague-Dawley rats. Animals were administered FK 506 and subjected to 60 min of renal warm ischemia by temporary occlusion of the renal artery and vein. No significant differences in serum creatinine levels among rats subjected to renal ischemia, FK 506, or FK 506 vehicle (methanol and 5% dextrose in water) were demonstrated. In contrast, FK 506 administration (4 mg/kg intraperitoneally) in combination with renal warm ischemia resulted in significant deterioration of renal function with peaking of serum creatinine on day 2. The timing of FK 506 administration relative to renal ischemia did not significantly affect serum creatinine levels. Rats that received FK 506 either 24 hr pre-ischemia, 4 hr pre-ischemia, 4 hr post-ischemia, or 24 hr post-ischemia all showed similar serum creatinine levels on day 2 (3.85 +/- 0.9, 4.7 +/- 0.5, 3.8 +/- 0.9, and 5.1 +/- 0.6 mg/dl, respectively, p = NS). In all animals, serum creatinine returned to baseline values by day 10. Histopathologic examination of kidneys revealed tubular atrophy and dilatation with tubular calcifications at the corticomedullary junction in FK 506 treated animals with or without ischemia. Our data suggest the timing of FK 506 administration in rats subjected to renal warm ischemia does not influence the extent of renal injury with an equally deleterious effect seen when administered within a 24 hr period of an ischemic event. Changes in kidney morphology, however, were seen in all FK 506 treated rats, with or without a period of warm ischemia.
在Sprague-Dawley大鼠中研究了FK 506（他克莫司）给药时间对肾功能及肾热缺血恢复的影响。给动物施用FK 506，并通过暂时阻断肾动脉和静脉使其经历60分钟的肾热缺血。结果显示，经历肾缺血、FK 506或FK 506赋形剂（甲醇和5%葡萄糖水溶液）的大鼠之间血清肌酐水平无显著差异。相比之下，FK 506给药（腹腔注射4mg/kg）联合肾热缺血导致肾功能显著恶化，血清肌酐在第2天达到峰值。FK 506给药相对于肾缺血的时间对血清肌酐水平无显著影响。在缺血前24小时、缺血前4小时、缺血后4小时或缺血后24小时接受FK 506的大鼠在第2天的血清肌酐水平均相似（分别为3.85±0.9、4.7±0.5、3.8±0.9和5.1±0.6mg/dl，p=无显著性差异）。在所有动物中，血清肌酐在第10天恢复到基线值。对肾脏的组织病理学检查显示，在接受或未接受缺血处理的FK 506处理动物中，肾脏出现肾小管萎缩和扩张，在皮质髓质交界处有肾小管钙化。我们的数据表明，在经历肾热缺血的大鼠中，FK 506给药时间不影响肾损伤程度，在缺血事件24小时内给药时均有同等有害作用。然而，在所有接受FK 506处理的大鼠中，无论是否经历一段时间的热缺血，均可见肾脏形态变化。
