Study of the liver tshemra/reperfusion injury recovery of the nepotocyte and sinnsoidol endotholial cell : invefvement of apoptosis and bile acrd depondent and indepondest ble flow.

肝细胞和辛索醇内皮细胞肝损伤/再灌注损伤恢复的研究：细胞凋亡和胆汁酸依赖和不依赖的胆流的影响。

• 批准号: 13671219
• 负责人: IMAMURA Hiroshi
• 金额: $ 2.24万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671219/
• 关键词: apoptosis; necrosis; liver regeneration; sinusoidal endothelial cell; v,I-67; caspase-3; 肝阻血再灌流障害; 類洞内皮細胞; カスパーゼ

Background and aim : We investigated the chronological profile of graft damage and recovery after liver cold ischemia-reperfusion (I/R) injury, paying particular attention to the role of apoptosis on hepatocyte and sinusoidal endothelial cell (SEC) damage. Methods : Male Lewis rats underwent re-arterialized orthotopic liver transplantation (OLT) using grafts subjected to a short period (UW1h) and to prolonged (UW16h) cold preservation. Experiments were performed immediately after preservation, 4h, 24h, 3days and 7days after reperfusion. At each time point, graft function, the incidence of apoptotic cells, expression of the epitope recognized by SEHL (a monoclonal antibody specific to rat SECs) and the incidence of proliferating cells was estimated. Results: In the UW16h group, the proportion of apoptotic SECs was markedly elevated at 4h. The incidence of hepatocyte apoptosis was very low, although massive hepatocyte necrosis was evident at 24h. The incidence of proliferating hepatocytes and SECs peaked at 3days and then returned to normal by 7days. Expression of SE-1was reduced immediately after preservation, followed by a marked reduction at 4h and 24h after reperfusion and then expression returned to normal by 7days. Conclusion : While SEC apoptosis was induced in the early phase of cold I/R injury, hepatocyte damage developed without the occurrence of apoptosis. Regeneration of both hepatocytes and SECs following cold I/R injury peaked 3days and was complete by 7days, whereas functional recovery of these cell populations was complete 3days after reperfusion.

背景和目标：我们研究了肝脏冷缺血再灌注（I/R）损伤后移植物损伤和恢复的时间曲线，特别注意细胞凋亡对肝细胞和窦状隙内皮细胞（SEC）损伤的作用。研究方法：雄性刘易斯大鼠进行了再动脉化原位肝移植（奥尔特），移植物经过短期（UW 1h）和长期（UW 16 h）冷保存。分别于保存后即刻、再灌注后4 h、24 h、3d、7 d进行实验。在每个时间点，估计移植物功能、凋亡细胞的发生率、SEHL（对大鼠SEC特异性的单克隆抗体）识别的表位的表达和增殖细胞的发生率。结果：UW 16 h组，4 h时凋亡的SEC比例明显升高。肝细胞凋亡的发生率很低，但在24 h时明显出现大量肝细胞坏死。增殖的肝细胞和SEC的发生率在3d达到高峰，然后在7 d恢复正常。SE-1表达在保存后即刻即开始下降，再灌注4 h和24 h明显下降，7 d后恢复正常。结论：冷I/R损伤早期诱导SEC细胞凋亡，但肝细胞损伤的发生并不伴随着凋亡的发生。冷I/R损伤后，肝细胞和SEC的再生在3d达到高峰，7 d完全，而这些细胞群的功能在再灌注后3d完全恢复。

项目成果

Imamura H, Matsuyama Y et al.: "Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy"38. 200-207 (2003)

Imamura H、Matsuyama Y 等人：“肝切除术后肝细胞癌早期和晚期肝内复发的风险因素”38。

Miyagawa Y, Imamura H et al.: "Fate of hepatucyte and sinusoidal lsulingcell function and kinetics after ettended cold preservation and transplantation at the rat liver"Liver Transplantation. 8. 370-381 (2002)

Miyakawa Y、Imamura H 等人：“大鼠肝脏冷藏和移植后肝细胞和肝窦炎症细胞功能和动力学的命运”肝移植。

Imamura H, Matsuyama Y, et al.: "Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy"Journal of Hepatology. 38. 200-207 (2003)

Imamura H、Matsuyama Y 等人：“肝切除术后肝细胞癌早期和晚期肝内复发的危险因素”肝脏病学杂志。

Miyagawa Y, Imamura H, Soeda J, Matsunaga K, Mochida S, Fujiwara K, Matsuyama Y, and Kawasaki S: "Fate of hepatocyte and sinusoidal lining cell function and kinetics after extended cold preservation and transplantation of the rat liver"Liver Trasnplantati

Miyakawa Y、Imamura H、Soeda J、Matsunaga K、Mochida S、Fujiwara K、Matsuyama Y 和 Kawasaki S：“大鼠肝脏长期冷藏和移植后肝细胞和肝窦衬里细胞功能和动力学的命运”肝脏移植

Y.Miyagawa, H.Imamura, et al.: "Fate of Hepatocyte and Sinusoidal Lining Cell Function and Kinetics After Extended Cold Preservation and Tranaplantation of the Rat Liver"Liver Transpl. 8(in press). (2000)

Y.Miyakawa、H.Imamura 等人：“大鼠肝脏长期冷藏和移植后肝细胞和正弦衬里细胞功能和动力学的命运”肝移植。