Sakr M F, Zetti G M, Hassanein T I, Farghali H, Nalesnik M A, Gavaler J S, Starzl T E, Van Thiel D H
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Hepatology. 1991 May;13(5):947-51.
The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting.
在大鼠三分之二肝部分切除术后，对未切除肝脏进行60分钟缺血处理，研究FK 506对肝脏再生的影响。将动物分为三组，每组10只大鼠。第1组（对照组）在缺血诱导后30分钟静脉注射0.5毫升生理盐水。第2组和第3组分别在肝脏缺血诱导后30分钟和24分钟前静脉注射FK 506（0.3毫克/千克）。测定每只动物肝脏的ATP含量以及血清中ALT和乳酸脱氢酶的水平。此外，在肝脏缺血后每隔24小时定期测定残余肝脏的组织学外观和有丝分裂活性。所有10只对照动物在72小时内死亡。FK 506治疗使第2组和第3组的存活率提高（分别为30%和80%）。FK 506治疗动物存活率的提高体现在肝脏ATP含量的恢复、血清中ALT和乳酸脱氢酶水平的降低、肝坏死和中性粒细胞浸润的改善以及肝脏有丝分裂活性的增加。这些结果表明，FK 506可减轻与缺血/再灌注相关的肝损伤，并对肝细胞再生具有强大的刺激作用，这可能使其在器官移植前给予器官供体时作为一种肝保护剂具有价值。
