Study of assisted liver transplantation for acute liver failure -Development of xeno auxiliary liver transplantation-

我们研究了动物辅助异位肝移植（ALT），以开发一种急性和亚急性肝衰竭的生命支持方法。首先通过肝外门静脉阻塞大鼠模型进行实验研究，以评估ICG清除物质（rk1000）的无创方法。这个工具是非常有用的，特别是在小动物，评估肝功能，而不取样外周血。在本项目的第二部分，使用袖带应用建立了一个简单的大鼠ALT模型。本实验以先天性高胆红素血症大鼠为实验对象，观察正常肝脏瞬时停置的影响。与Wistar大鼠正常肝脏异位移植的Gunn大鼠血清胆红素浓度显著降低，维持在正常水平。移植1个月后安全进行了移植物切除术，但总胆红素水平未恢复到Gunn大鼠的术前水平。肝干细胞有可能包含在ALT肝中，并生成酶生成细胞。最后，从小鼠或仓鼠到大鼠进行异种ALT移植。发现胆道重建有困难。环磷酰胺联合FK-506治疗可有效延长移植物存活时间。

We studied auxiliary heterotopic liver transplantation (ALT) in animals to develop a life support method for acute and subacute liver failure.An experimental study on a rat model of extrahepatic portal obstruction was firstly performed to evaluate non-invasive method of ICG clearance mater (RK 1,000). This tool was very useful, especially in small animals, for evaluation of liver function without sampling of peripheral blood.In the second part of this project, a simple ALT model was established in rats using the cuff application. Effects of transient parking of normal liver were tested in congenitally hyperbilirubinemic Gunn rats. Serum bilirubine concentrations of Gunn rats, transplanted heterotopically with normal livers of Wistar rats, were dramatically reduced and maintained to the normal levels. The graftectomy was performed safely 1 month after transplantation, but total bilirubine levels were not returned to the preoperative value of Gunn rats. There was a possibility that hepatic stem cells were included in ALT liver and generated to enzyme producing cells.Finally, xenogenic ALT was performed from mice or hamsters to rats. A difficulty was found in reconstration of biliary tract. The combination therapy of cyclosphamide plus FK-506 was effective for prolongation of the graft survival.