門脈結紮による肝再生過程における線維芽細胞の役割解明～肝切除適応の拡大を目指して

阐明成纤维细胞在门静脉结扎诱导肝脏再生过程中的作用——旨在扩大肝切除术的应用

• 批准号: 22K08733
• 负责人: 小山 幸法
• 金额: $ 2.75万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K08733/
• 关键词: 肝臓再生; 門脈結紮; 門脈塞栓; 肝線維芽細胞; 肝星細胞; 肝臓萎縮; 線維芽細胞; 星細胞

肝臓切除後の術後肝不全予防のため、術前に門脈塞栓による肝臓再生の後手術を行う手法は日常臨床で行われている。しかしながら、再生を制御するメカニズムは未解明であるし、臨床においても門脈塞栓を行ったものの肝臓の再生が十分ではなく肝切除を断念する症例も経験する。門脈血流遮断後の肝臓内の線維芽細胞が肝臓再生にどのような役割を果たすのかという問いに挑戦したい。門脈結紮後の肝臓再生のメカニズムを明らかにすることは、直接的には上述の肝臓切除術後の肝不全の予防に寄与するばかりか、将来的にはいったん非代償性の肝不全に陥った肝不全の治療法開発、肝臓再生のメカニズムを解明するうえで極めて重要な知見となると考える。本研究はマウスの門脈結紮モデルにおいて肝臓再生過程における線維芽細胞の役割を解明することを目的とする。Aim1として門脈結紮後の肝再生過程における線維芽細胞の種類を特定し、その活性化マーカー発現パターンを特定することを目標とした。まず、マウスの肝中葉／左葉への門脈枝を8-0 Proleneで結紮し、肝右葉の肥大・肝中葉／左葉の萎縮を導くモデルを作成した。本モデルでは人の門脈塞栓後に観察されるように全肝重量における肝右葉（非結紮側）の割合は著明に増大し、肝左葉中葉（結紮側）は萎縮を認めた。１型コラーゲンプロモーター下に緑色蛍光蛋白（GFP）を発現するトランスジェニックマウスに対し、この方法で門脈結紮を施し、GFP陽性細胞（コラーゲン発現細胞）の増加を確認した。このことは肝切除後の再生過程でも観察されたが、門脈結紮モデルにおいても肝再生にコラーゲン発現細胞が重要な役割を果たしている可能性が示唆される。さらに門脈結紮後に現れる線維芽細胞の欠失実験が重要な意味をもつこととなる。現在予定していた実験計画の通りに実験進行中である。

After hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention and treatment of hepatic insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency after hepatectomy, The system and control of liver regeneration were not clear, and the bed was filled with plug. The liver was regenerated. After the blood flow was occluded, the liver was regenerated and the liver was regenerated. After the blood flow was cut off, the liver was regenerated. After the treatment of liver regeneration, it is clear that the prevention of liver insufficiency after hepatectomy, the prevention of liver insufficiency and the treatment of non-generative liver insufficiency, liver regeneration and liver regeneration are very important. The purpose of this study is to investigate the process of liver regeneration in the process of maintaining germ cells. After Aim1 treatment, the process of liver regeneration is critical to maintain germ-specific cells, and the activation of germ cells has a significant effect on specific liver regeneration. The middle and left sides of the liver were divided into 8-0 Prolene results, the right side of the liver was hypertrophic, and the left side of the liver was damaged. After the embolization, we need to check the weight of the whole liver. the right side of the liver (not the results) is divided into the right side of the liver and the left side of the liver (results). The color light protein (GFP) was detected in the type 1 system. The results of the test, the method of the test, and the confirmation of the GFP cell were not detected. After hepatectomy, the process of liver regeneration after hepatectomy was monitored, and the results showed that the possibility of liver regeneration was significantly higher than that of liver regeneration. If you don't have enough information to maintain your germ cell, if you don't have enough information, it means that you don't know if it's important. It is now expected that the project will be in progress.