Kahn D, Makowka L, Lai H, Eagon P K, Dindzans V, Starzl T E, Van Thiel D H
Department of Surgery, University of Pittsburgh, Pennsylvania.
Dig Dis Sci. 1990 Mar;35(3):392-8. doi: 10.1007/BF01537420.
A number of mechanisms participate in the hepatic injury that occurs during and following liver transplantation. A normal allograft regenerative response is probably essential for a successful transplant outcome. In this study, the effect of cyclosporine, a potent immunosuppressant used routinely after liver transplantation, on the regenerative response of the liver after partial hepatectomy was investigated. Male Wistar rats were pretreated for one week with either cyclosporine or the olive oil vehicle and were subjected to either a two-thirds partial hepatectomy or a sham operation. Animals were sacrificed at various times postoperatively and the remnant livers were weighed to determine the liver weight to body weight ratio, two biochemical measures of a regenerative response (cytosolic ornithine decarboxylase activity and thymidine kinase activity), and the hepatic content of estrogen and androgen receptors, as the content of these receptors has been shown to modulate, at least in part, the subsequent hepatic regenerative response. The preoperative hepatic cytosol content of ornithine decarboxylase, thymidine kinase, and estrogen receptor was significantly greater (P less than 0.05) in rats pretreated with cyclosporine than in those treated with the vehicle alone. A significant increase in ornithine decarboxylase and thymidine kinase activities occurred after partial hepatectomy in both the cyclosporine-pretreated and vehicle-pretreated animals. The absolute levels for each parameter were also greater in the cyclosporine-treated animals than in the vehicle-treated controls at 24 hr after partial hepatectomy (P less than 0.05). The pattern of change in the hepatic cytosolic content of estrogen and androgen receptors in both groups of animals was comparable with those described previously for regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)
多种机制参与肝移植术中及术后发生的肝损伤。正常的同种异体移植再生反应可能是移植成功的关键。本研究调查了肝移植后常规使用的强效免疫抑制剂环孢素对部分肝切除术后肝脏再生反应的影响。雄性Wistar大鼠用环孢素或橄榄油载体预处理一周，然后进行三分之二部分肝切除术或假手术。术后在不同时间点处死动物，称量残余肝脏重量以确定肝重与体重之比、两种再生反应的生化指标（胞质鸟氨酸脱羧酶活性和胸苷激酶活性）以及肝脏中雌激素和雄激素受体的含量，因为这些受体的含量已被证明至少部分调节随后的肝脏再生反应。术前，用环孢素预处理的大鼠肝胞质中鸟氨酸脱羧酶、胸苷激酶和雌激素受体的含量显著高于仅用载体处理的大鼠（P<0.05）。部分肝切除术后，环孢素预处理组和载体预处理组动物的鸟氨酸脱羧酶和胸苷激酶活性均显著增加。部分肝切除术后24小时，环孢素处理组动物各参数的绝对水平也高于载体处理的对照组（P<0.05）。两组动物肝脏胞质中雌激素和雄激素受体含量的变化模式与先前描述的再生肝脏的变化模式相似。（摘要截断于250字）
