Research for investigating treatment of fulnilnant hepatic failure : An experimental study of auxiliary temporal partial orthotopic liver transplantation using living-donor partial liver

全面性肝衰竭治疗研究：活体部分肝辅助颞部部分原位肝移植的实验研究

基本信息

批准号：
08557078
负责人：
NAKANO Hiroshi
金额：
$ 6.27万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

(Background and Aim) Fulminant hepatic failure has been a fatal disease and has had an extremely poor prognosis. However, prognosis of fulminant failure was recently improved up to 50% of survival after orthotopic liver transplantation. An alternative, auxiliary temporal partial orthotopic liver transplantation (ATPOLT), is mole useful since ATPOLT can allow two liver transplantations and can avoid immunosuppression therapy after recovery of patients. To introduce ATPOLT for fulminant hepatic failure in Japan, living-related partial liver should be introduced. The aim of the present study was to investigate what kinds of supporting therapy are needed for ATPOLT using living-related liver in pigs.(Materials and Methods) Pigs were fed a choline-methionine deficient diet for 2 months. Then, the common bile duct was ligated through laparotomy. A fulminant hepatic failure model was produced 1 week after bile duct ligation (Recipient pigs). The living-related partial left lobe liver was proc … More ured from normal pigs (Donor pigs). ATPOLT was immediately performed for the recipient pigs according to the method of Boudjema et al. In Group A (n = 5), no treatment was added after ATPOLT. In Group B (n = 5), a free radical scavenger, N-acetylcysteine (150 mg/kg/day) and anti-intercellular adhesion molecule 1 monoclonal antibody (0.8 mg/kg/day) were administered day by day after ATPOLT.(Results) In Group A, all pigs died on 3 days after ATPOLT. In Group B, all pigs survived during 3 days after ATPOLT. Serum α-glutathione S transferase concentration, which can indicate hepatocellular injury just before a few hours, was significantly higher in Group A than in Group B after the postoperative day 2 (p<0.05). Prothrombin time, concentrations of serum total bilirubin, that of serum reduced glutathione were significantly improved in Group B than in Group B.(Conclusion) As shown in Group A, ATPOLT could not result in long-term survival in pigs with fulminant hepatic failure. However, immediate treatment using the free radical scavenger and the monoclonal antibody inhibiting adhesion between neutrophils and endothelial cells can inhibit non-function of the graft liver and can allow long-term survival of the animals with fulminant hepatic failure. Less

（背景和目的）暴发性肝衰竭是一种致命的疾病，预后极差，但最近在原位肝移植后，暴发性肝衰竭的生存率提高了 50%。（ATPOLT），是摩尔有用的，因为 ATPOLT 可以允许两次肝移植，并且可以避免患者康复后的免疫抑制治疗。日本爆发性肝衰竭，应引入活体部分肝，本研究的目的是探讨使用活体相关肝对猪进行 ATPOLT 需要什么样的支持治疗。（材料与方法）胆碱-蛋氨酸缺乏饮食2个月，然后通过剖腹手术结扎胆总管，建立暴发性肝衰竭模型。（受体猪）从正常猪（供体猪）中获取活体相关的部分左叶肝脏，并根据 Boudjema 等人的方法立即对受体猪进行 ATPOLT。），B组（n = 5）后不添加自由基清除剂，N-乙酰半胱氨酸（150 mg/kg/天）和抗细胞间质瘤。 ATPOLT后逐日给予粘附分子1单克隆抗体(0.8mg/kg/天)。(结果)A组所有猪均在ATPOLT后3天内死亡。B组所有猪在ATPOLT后3天内均存活。术后第 2 天后，A 组的血清 α-谷胱甘肽 S 转移酶浓度显着高于 B 组，该浓度可表明几小时前的肝细胞损伤(p<0.05) B组的凝血酶原时间、血清总胆红素浓度、血清还原型谷胱甘肽浓度均较B组显着改善。(结论)如A组所示，ATPOLT不能导致患者长期生存。然而，患有暴发性肝衰竭的猪，立即使用自由基清除剂和抑制中性粒细胞与内皮细胞之间粘附的单克隆抗体进行治疗可以抑制肝功能的丧失。移植肝脏可以使患有暴发性肝衰竭的动物长期存活。