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

急性肝功能衰竭辅助肝移植研究-异种辅助肝移植的进展-

• 批准号: 07671418
• 负责人: KASAHARA Kogorou
• 金额: $ 0.83万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671418/
• 关键词: Auxiliary liver transplantation; Acute liver failure; Xeno transplantation; 動物モデル; 門脈-静脈シャント

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.

为了建立一种治疗急性和亚急性肝功能衰竭的生命支持方法，我们对辅助性异位肝移植(ALT)动物模型进行了研究。首次对大鼠肝外门静脉阻塞模型进行了实验研究，以评价ICG清除物质(RK1,000)的无创性方法。这个工具非常有用，特别是在小动物中，在不采集外周血的情况下评估肝功能。在本项目的第二部分，使用袖带应用程序在大鼠身上建立了一个简单的ALT模型。在先天高胆红素血症的Gunn大鼠上测试了正常肝脏的短暂停放效应。Gunn大鼠与Wistar大鼠正常肝脏异位移植后，血清胆红素浓度显著降低并维持在正常水平。移植后1个月移植物切除安全，但总胆红素水平未恢复到Gunn大鼠的术前水平。有一种可能性是肝干细胞被包含在ALT肝脏中并生成产酶细胞。最后，从小鼠或仓鼠到大鼠进行异种ALT。胆道重建术有困难。环磷酰胺联合FK-506能有效延长移植物存活时间。

项目成果

Kobayashi E: "Experimental transplantation models in the rat using cuff technique:The merits and pitfalls." Recent advance in experimental microsurgery. 2. 151-161 (1994)

Kobayashi E：“使用袖带技术的大鼠实验移植模型：优点和缺点。”

Kobayashi E: "Experimental transplantation models in the rat using cuff technique : The merits and pitfalls." Recent advance in experimental microsurgery. 2. 151-161 (1994)

Kobayashi E：“使用袖带技术的大鼠实验移植模型：优点和缺点。”