生体肝移植の手技を用いた脂肪肝ドナーの病態解析と治療法の実験的検討

活体肝移植技术脂肪肝供者的病理分析及治疗方法的实验研究

• 批准号: 09770960
• 负责人: 長崎 秀彰
• 金额: $ 1.34万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09770960/
• 关键词: 肝脂肪変性; 生体部分肝移植; 閉塞性黄疸; N-acetylcysteine; 肝oxidative stress; 肝microcirculatory flow; mitochondrial GSSG; GSH; 好中球活性酸素産生

本研究は,閉塞性黄疸下において生体部分肝移植を施行した場合、ドナー肝の高度脂肪変性が来すとされる肝機能障害発症のメカニズムとその病態改善の治療方法を検討することを目的としている.ビーグル犬の肝外胆管を結紮、閉塞性黄疸を作成し、ストレプトゾトシン100mg/kgを1週間前に投与し、40〜60%の中等度脂肪変性肝を作成した。黄疸ビーグル犬を再開腹、肝臓全摘出し脂肪変性肝モデルの肝左葉をドナー肝として、非投与群、NAC群(N-acetylcysteine(NAC)ドナー肝虚血15分前より150mg/kg/hr持続投与、再灌流後50mg/kg/hr4時間投与を3日間)、PGE1群(PGE1を0.05mg/kg/minを再灌流後3時間持続投与を3日間)、PGE1+NAC群とを作成した。門脈血流量、肝組織血流量は非投与群に比べ他の3群は上昇し、また血中cGMP濃度はNAC群、PGE1+NAC群で上昇を認め、cAMP濃度はPGE1群、PGE1+NAC群で上昇をみとめた。肝機能改善の指標であるATPは非投与群と比べNAC群、PGE1群、PGE1+NAC群で改善傾向を認め、Oxidative stressの指標とされるグルタチオン(還元型GSH、酸化型GSSG)では、GSH/GSSGはNAC群、PGE1+NAC群で上昇傾向を認めた。ミトコンドリアのグルタチオン濃度は、NAC群、PGE1+NAC群で上昇傾向を認めた。以上より肝血流の改善は、術後の肝機能の改善に寄与することが示唆され、またNACの投与は肝組織のOxdative stressの改善作用を有することが示唆された。

In this study, partial orthotopic liver transplantation under obstructive jaundice was performed to improve the symptoms of partial liver transplantation. in this study, partial liver transplantation under obstructive jaundice was performed to prevent and treat the disease. The results of extrahepatic bile duct, occlusive jaundice, 100mg/kg and moderate fatty liver of 40-60% were observed in dogs. In jaundiced dogs, laparotomy was performed, total hepatectomy was performed on the left side of the liver, and no injection was given to the left side of the liver. 150mg/kg/hr was administered 15 minutes before N-acetylcysteine (NAC), 50mg/kg/hr4 3 days after reperfusion), PGE 1 (PGE1 0.05mg/kg/min 3 days after reperfusion), and PGE1+ NAC groups were established. The blood flow of liver tissue and blood flow of liver tissue were not compared with those of other groups. The levels of cGMP in blood, NAC, PGE1+NAC, PGE1 and PGE1+NAC in serum were significantly higher than those in other groups. The liver machine can improve the comparison between ATP group and population, NAC group, PGE1 group, PGE1+NAC group, Oxidative stress group (meta-GSH, acidified GSSG) group, GSH/ GSSG group, PGE1+NAC group. Please tell me that you are not aware of the situation on the NAC group, PGE1+NAC group, and NAC group. The improvement of hepatic blood flow and the ability of post-operative liver function to improve liver blood flow and liver tissue Oxdative stress were significantly improved in both groups.

项目成果

Nagasaki H,et al.: "Augmentation of mitochondrial glutathione by S-adenosyl-L-methionine in ischemia-reperfusion injury of the rat steatotic liver induced by choline-methionine deficient diet." European Surgical Research. 30. 34-42 (1998)

Nagasaki H 等人：“S-腺苷-L-蛋氨酸在胆碱-蛋氨酸缺乏饮食诱导的大鼠脂肪肝缺血再灌注损伤中增强线粒体谷胱甘肽。”

Nagasaki H,et al.: "The efficiency of N-acetylcysteine preconditioning against reperfusion injury after prolonged cold ischemia in aseverely glutathione-decreased rat liver prodeued by buthionine sulphoximine." European Journal of Surgery. (in press).

Nagasaki H 等人：“N-乙酰半胱氨酸预处理对丁硫氨酸亚磺酰亚胺引起的谷胱甘肽严重减少的大鼠肝脏长期冷缺血后再灌注损伤的效率”。

Nagasaki H,et al.: "The effect of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by choline-methionine deficient diet." Hepatology. 26. 670-678 (1997)

Nagasaki H等人：“N-乙酰半胱氨酸和抗细胞间粘附分子-1单克隆抗体对胆碱甲硫氨酸缺乏饮食引起的大鼠脂肪肝缺血再灌注损伤的作用”。

Nagasaki H,et al: "The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by choline-methionine deficient diet." Hepatology. 26. 670-678 (1997)

Nagasaki H等人：“N-乙酰半胱氨酸和抗细胞间粘附分子-1单克隆抗体对胆碱蛋氨酸缺乏饮食引起的大鼠脂肪肝缺血再灌注损伤的影响”。

Nagasaki H,et al: "N-acetylcysteine and anti-ICAM-1 monoclonal antibody reduce ischemia-reperfusion injury of the rat steatoic liver" Transpl.Proc.30. 3763 (1998)

Nagasaki H等人：“N-乙酰半胱氨酸和抗ICAM-1单克隆抗体减少大鼠脂肪肝的缺血再灌注损伤”Transpl.Proc.30。