肝移植における肝障害発生機序の解明と新しい肝viability判定法 の検討 (温阻血、保存ならびに血流再開時の肝障害のメカニズムの解析と極微弱発光 測定法の検討)

肝移植中肝损伤机制的阐明和测定肝脏活力的新方法的研究（热缺血、保存和恢复血流时肝损伤的机制分析以及极弱发光测量方法的研究）

• 批准号: 63570586
• 负责人: 佐々木 崇
• 金额: $ 1.28万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570586/
• 关键词: 肝viability; Primay graft failure; 肝ミ トコンドリア機能; 呼吸調節率 (RCR); 肝類洞内皮障害; 極微弱発光 (CL)

肝移植における移植前ドナー肝のviabilityの評価ならびに肝 移植早期に出現する、いわゆるprimary graft failureの発生 機序の解明のため研究を行ない、以下の成果を得た。1) 移植肝障害発生機序を生化学的、組織学的に検討を行なった結果、ミトコン ドリア機能を指標した生化学的検索では、一般的な保存方法のもとでは12時間まで 機能が保たれており、組織学的にも肝細胞内小器官の構造やミトコンドリアの計測上 の値も同じ12時間までは変化がなかった。これに対し、肝類洞内皮細胞は、12時 間ではsecondary lysosomeを生じ、師板構造は乱れてporeが 強く変化しており、ディッセ腔の開大にともなってsinusoidが狭小化してく る所見が得られ、この状態で移植するとディッセ腔に血球成分がトラップされる所見 が得られた。この結果は、肝実質細胞は12時間ではよく保存されているが、血管内 皮障害を主とする血管系がこの時間ではすでに障害されており、移植後血流再開と同 時に急速に循環障害におちいるという一連の変化であり、primay graft failure発生の本体であろうとの重大な結果と考えられる。現在、血管内皮 障害を軽減する保存方法の開発に着手している。2) 移植肝viabilityの評価についてi) 呼吸調節率 (RCR) の検討 ii) 極微弱発生測定のそれぞれ異なった方法により興味ある結果を得た。とくに前 者は移植前の肝組織での結果が、移植成績と非常に良く相関することから実際の臨床 前の肝組織での結果が、移植成績と非常に良く相関することから実際の臨床に即、応 用可能であり、viability検索の重要な手段となり得る。後者は、保存肝、 温阻血肝をホモジェネイトレ、多分画における活性酵素による脂質過酸化の状態を極 微弱発生測定より検討している。いづれも障害肝では高値を示めすが、種々の条件制 定により大きく左右されることから、更に検討を行ない精度の向上をはかる。

The evaluation of liver viability before liver transplantation and the understanding of the mechanism of primary graft failure in the early stage of liver transplantation were conducted. The following results were obtained. 1)Liver transplantation disorder development sequence: biochemical, histological, functional, biochemical, general preservation method: functional, histological, intracellular, small organ structure: histological, functional, histological, functional, biological, biological, histological, biological, biological, In contrast, liver cavity-like endothelial cells were found to grow secondary lysosome at 12 o'clock, and the structure of the plate was changed from strong to narrow. The results showed that the liver cells were preserved for 12 days, and the vascular system was damaged for 12 days. The blood flow was reopened after transplantation. At the same time, the rapid circulation was damaged for 12 days. At present, the development of preservation methods to reduce vascular endothelial damage is under way. 2)Evaluation of liver graft viability (i) Evaluation of respiratory regulation rate (RCR)(ii) Evaluation of particulate matter development (iii) Evaluation of liver graft viability (iv) Evaluation of respiratory regulation rate (RCR)(iii) Evaluation of liver graft viability (iv) Evaluation of respiratory regulation rate (RCR)(iv) Evaluation of respiratory regulation rate (RCR)(iv) Evaluation of liver graft viability (iv) Evaluation of respiratory regulation rate (RCR)(iv) Evaluation of respiratory regulation rate (RCR)(iv) Evaluation of liver graft viability (iv) Evaluation of respiratory regulation rate (RCR)(iv) Evaluation of liver graft viability (iv) Evaluation of liver graft viability (iv) Evaluation of respiratory regulation rate (RCR)(iv) Evaluation of respiratory regulation rate (iv) Evaluation of respiratory regulation rate (iv) Evaluation of liver graft viability (iv) Evaluation of liver graft viability (iv) Evaluation of respiratory regulation rate (iv) Evaluation of liver graft viability (iv) Evaluation of liver graft viability (iv) Evaluation of respiratory regulation rate (iv) Evaluation of The results of liver tissue before transplantation are very well correlated with the results of transplantation. The results of liver tissue before transplantation are very well correlated with the results of transplantation. The results of liver tissue before transplantation are very well correlated with the results of liver tissue before transplantation. The results of liver tissue before transplantation are very well correlated with the results of transplantation. The results of liver tissue before transplantation are very well correlated with the results of liver tissue before transplantation. The results of liver tissue before transplantation are very well correlated with the results of liver tissue before transplantation. The results of liver tissue before transplantation. The results of liver tissue before transplantation are very well correlated with the results of liver tissue before transplantation. The latter is characterized by very weak detection of lipid peroxidation in liver preservation, thermo-stable liver, and multi-component active enzymes. In addition to the above, the accuracy of the method is also discussed.