Mazzaferro V, Porter K A, Scotti-Foglieni C L, Venkataramanan R, Makowka L, Rossaro L, Francavilla A, Todo S, Van Thiel D H, Starzl T E
Department of Surgery, School of Pharmacy, University Health Center of Pittsburgh, Pa.
Surgery. 1990 May;107(5):533-9.
The effect of cyclosporine on liver regeneration has been investigated in 25 dogs that underwent an end-to-side portacaval shunt (Eck fistula) followed by 4 days continuous infusion of the drug into the left branch of the portal vein. Three different cyclosporine infusion rates were used: 0.06, 0.6, and 4.0 mg/kg/day. Control animals received the intravenous vehicle of cyclosporine at the same rate as the treated animals; a second control group received insulin, 0.42 units/kg/day. Hepatocyte 3H-thymidine-labeled mitoses (index of hyperplasia) and hepatocyte volume (index of hypertrophy) were studied in the left (infused) and right (control) lobes in each animal. Cyclosporine vehicle had no measurable effect on hepatocytes that suffered typical atrophy and moderate increase in mitotic index after the Eck fistula. Cyclosporine infusion stimulated cell renewal significantly and restored hepatocyte size in the infused lobes with a dose-response relation. Similar positive effects were observed in the right (nonperfused) lobes, although they were less than those in the left (infused) lobes. This was because of an unmistakable spillover of cyclosporine from the infused lobes, especially in the large-dose group. No sign of hepatotoxicity was detected at any cyclosporine infusion rate. Cyclosporine has a remarkable hepatotropic effect that may be helpful in the context of liver transplantation.
在25只接受端侧门腔分流术（埃克瘘）的犬中研究了环孢素对肝脏再生的影响，术后连续4天将该药物经门静脉左支输注。使用了三种不同的环孢素输注速率：0.06、0.6和4.0毫克/千克/天。对照动物以与治疗动物相同的速率接受环孢素的静脉载体；第二个对照组接受胰岛素，0.42单位/千克/天。在每只动物的左（输注）叶和右（对照）叶中研究了肝细胞3H-胸腺嘧啶标记的有丝分裂（增生指数）和肝细胞体积（肥大指数）。环孢素载体对在埃克瘘后出现典型萎缩和有丝分裂指数适度增加的肝细胞没有可测量的影响。环孢素输注显著刺激细胞更新，并使输注叶中的肝细胞大小恢复，呈剂量反应关系。在右（未灌注）叶中也观察到类似的积极作用，尽管比左（输注）叶中的作用小。这是因为环孢素从输注叶有明显的溢出，尤其是在大剂量组。在任何环孢素输注速率下均未检测到肝毒性迹象。环孢素具有显著的亲肝作用，这在肝移植的情况下可能是有益的。
