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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557078/
• 关键词: fulminant hepatic failure; α-glutathione S transferase; choline-methionine deficient diet; N-acetylcysteine; reduced glutathione; anti-intercellular adhesion molecule; auxiliary temporal partial orthotopic liver transplantation; N-acetylcysteine

(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

（背景和目标）暴发性肝衰竭一直是一种致命的疾病，预后极差。然而，在原位肝移植后，最近将暴发性衰竭的预后提高了50％。替代性辅助临时部分原位肝移植（ATPOLT）是有用的，因为ATPolt可以允许两次肝移植，并且可以避免在患者恢复后避免免疫抑制治疗。为了引入日本暴发性肝衰竭的ATPOLT，应引入与生活有关的部分肝脏。本研究的目的是研究使用与猪中的生活相关的肝脏ATPolt需要哪种支持疗法。（材料和方法）猪被胆碱甲硫代氨酸饮食喂2个月。然后，通过剖腹手术结扎了常见的胆管。在胆管连接后1周产生了暴发性肝衰竭模型（受体猪）。与生活相关的部分左叶肝脏是Proc…更多的是正常的猪（供体猪）。根据Boudjema等人的方法，立即为受体猪立即进行ATPolt。在A组（n = 5）中，ATPolt后未添加治疗。在B组（n = 5）中，一种自由基清除剂，N-乙酰半胱氨酸（150 mg/kg/day）和抗中细胞粘附分子1单克隆抗体（0.8 mg/kg/kg/kg/kg/kg）（每天通过ATPOLT每天按A ATPOLT每天按A at All All A All All All All All All All All All A Atpolt施用。在B组中，所有猪在Atpolt后3天内存活。血清α-谷胱甘肽的转移酶浓度可能在几个小时之前表明肝细胞损伤，A组在术后第2天后的B组显着高于B组（P <0.05）。凝血酶原的时间，血清总胆红素的浓度，血清减少的谷胱甘肽的浓度明显改善。但是，使用自由基清除剂和抑制嗜中性粒细胞和内皮细胞之间粘合剂的单克隆抗体的立即治疗可以抑制移植肝脏的非功能，并且可以允许动物以暴发性肝衰竭的长期存活。较少的

项目成果

Takeuchi S, Nakano H, et al.: "Predicting Survival and Postoperative Complications with Tc-GSA Liver Scintigraphy in Hepatocellular Carcinoma"Hepatogastroenterology. 46. 1855-61 (1999)

Takeuchi S、Nakano H 等人：“利用 Tc-GSA 肝脏闪烁扫描术预测肝细胞癌的生存和术后并发症”肝胃肠病学。

Baek Y, Nakano H, et al.: "Administration of Prostaglandin E1 Reduces Postoperative Hepatocellular Damage and Restores Hepatic Integrity in Patients Undergoing Hepatectomy"Hepatogastroenterology. 46. 1836-41 (1999)

Baek Y、Nakano H 等人：“给予接受肝切除术的患者服用前列腺素 E1 可减少术后肝细胞损伤并恢复肝脏完整性”肝胃肠病学。

Nakano H,et al.: "Dextran sulfate inhibits E-selectin-mediated neutrophil adhesion to endotoxin-activated vascular endothelial cells" Life Sci.64. 9-17 (1998)

Nakano H 等人：“硫酸葡聚糖抑制 E-选择素介导的中性粒细胞与内毒素激活的血管内皮细胞的粘附”Life Sci.64。

Kigawa G, Nakano H, et al.: "Improvement of portal hepatic microcirculatory tissue flow with N-acetylcysteine in dogs with obstructive jaundice produced by bile duct ligation"Eur J Surg. 166. 77-84 (2000)

Kikawa G、Nakano H 等人：“用 N-乙酰半胱氨酸改善因胆管结扎引起的梗阻性黄疸犬的门肝微循环组织流动”Eur J Surg。

Nakano H,et al: "Prognostic ebaluation of locally advanced gastric cancer patients with preoperative downstaging chemotherapy." Cancer Detect Prev. 20. 447-448 (1996)

Nakano H 等人：“术前降期化疗的局部晚期胃癌患者的预后评估。”