Starzl T E, Porter K A, Mazzaferro V, Todo S, Fung J, Francavilla A
Department of Surgery, University of Pittsburgh, PA 15213.
Transplantation. 1991 Jan;51(1):67-70. doi: 10.1097/00007890-199101000-00010.
Portacaval shunt (Eck fistula) in dogs causes hepatocyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this procedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of hepatocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506's efficacy for the treatment of chronic liver rejection. Also, the observations support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cytosolic binding sites of FK506, repatomycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.
犬的门腔分流术（埃克瘘）会导致肝细胞萎缩和细胞器破坏，同时肝细胞有丝分裂增加两倍。在对犬实施该手术后，将FK506注入结扎的左门静脉。在注入FK506的肝脏部分，肝细胞的大小、解剖质量和增殖能力均得到增强，且在未注入部分有显著的溢出效应。FK506的这些肝细胞营养特性可能部分解释了其治疗慢性肝排斥反应的疗效。此外，这些观察结果支持对该药物进行治疗自身免疫性肝病的试验，因为除了消除此类疾病的免疫起源外，还可能增强受损肝脏的修复和再生能力。最后，这些肝细胞营养特性是由可能调节酶顺反肽基 - 脯氨酰异构酶（PPIase）的药物所引发的一系列新出现的生物学效应的一部分，PPIase是FK506、雷帕霉素、环孢素以及可能尚未发现的其他免疫抑制药物胞质结合位点的主要成分。
