The modulation of transcription factor in liver regeneration after hepatic ischemia/reperfusion

转录因子在肝缺血/再灌注后肝再生中的调节

• 批准号: 17591373
• 负责人: KATO Atsushi
• 金额: $ 2.24万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591373/
• 关键词: hepatic ischemia; reperfusion; liver regeneration; transcription factor; cholestatic liver; hepatic stellate cell; endothelin-1; activin; follistatin; 阻血; 再灌流; サイトカイン; ケモカイン; 障害肝; 閉塞性黄疸; 内皮細胞

1. Liver regeneration after hepatic ischemia/reperfusion injury.Activin mRNA expression and serum levels of activin were increased within 1 hour of reperfusion. Follistatin protein levels in serum samples were also increased after reperfusion. These results indicate that activin inhibits initiation of regeneration in hepatocytes at early time point after hepatic ischemia/reperfusion. The activin-follistatin system is one of the important regulatory systems modulating regeneration processes of the liver.2. Hepatic ischemia/reperfusion injury alterations in experimental cholestasis.The mechanism of liver injury in cholestatic liver is not fully understood. Male C57BL/6 mice underwent common bile duct ligation and subsequently developed obstructive cholestasis. The mice were subjected to 90 minutes of partial hepatic ischemia followed by reperfusion. The survival rate of the mice with cholestatic livers after hepatic ischemia/reperfusion was lower than that of the mice with normal livers. … More Biochemical and histological analyses showed that the cholestatic mice had a much higher degree of hepatocellular injury after reperfusion than the normal mice. Neutrophil accumulation after reperfusion was significantly decreased in the cholestatic livers ; however, considerable microcirculatory disturbances were observed in cholestatic livers after reperfusion. Hepatic stellate cell activation and hepatic expression of endothelin-1 were evaluated by immunohistochemical staining in cholestatic livers after reperfusion. These observations were also associated with increased serum levels of endothelin-1. Hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver.3. Clinical examination of liver regeneration.Preoperative portal vein embolization (PVE) is an effective means of creating hypertrophy of future remaining liver, which leads to safety of extensive hepatectomy for hepatic malignancies. Hepatic response to PVE includes the induction of numerous mediators such as growth factors. However, the factors affecting liver regeneration after PVE are not clearly understood. Plasma VEGF levels were increased markedly after PVE and were maximal after 7 days of PVE. Plasma TGF-beta levels were also increased after PVE and peaked at 14 days. % increased liver volume was significantly correlated with plasma VEGF level after 7 days of PVE.. VEGF could affect the activation of regenerative cascade in hepatic remaining lobe after PVE.. Measurement of plasma VEGF levels after PVE may be a predictive factor of potential liver regeneration and may provide useful information to decide on the schedule of subsequent hepatectomy Less

1.肝缺血再灌注损伤后的肝再生：再灌注1小时内激活素mRNA表达和血清激活素水平增加。再灌注后，血清样品中卵泡抑素蛋白水平也增加。这些结果表明，激活素在肝缺血/再灌注后的早期时间点抑制肝细胞再生的启动。激活素-卵泡抑素系统是调控肝脏再生过程的重要调节系统之一.实验性胆汁淤积症肝脏缺血/再灌注损伤的改变胆汁淤积性肝脏损伤的机制尚不完全清楚。雄性C57 BL/6小鼠接受胆总管结扎，随后发生阻塞性胆汁淤积。使小鼠经受90分钟的部分肝缺血，然后再灌注。肝缺血再灌注后胆汁淤积性肝损伤小鼠的存活率低于正常肝损伤小鼠。 ...更多信息 生化和组织学分析表明，胆汁淤积小鼠在再灌注后肝细胞损伤程度明显高于正常小鼠。在胆汁淤积性肝脏中，再灌注后的神经元积聚显著减少;然而，在胆汁淤积性肝脏中观察到再灌注后相当大的微循环障碍。免疫组化染色观察再灌注后肝星状细胞的活化和内皮素-1的表达。这些观察结果也与内皮素-1的血清水平升高有关。肝星状细胞的活化和内皮素-1的增加在胆汁淤积性肝缺血/再灌注损伤中起重要作用.肝再生的临床检查：术前门静脉栓塞（PVE）是一种有效的手段，创造未来剩余的肝脏肥大，这导致广泛的肝切除术治疗肝脏恶性肿瘤的安全性。肝对PVE的反应包括诱导许多介质，如生长因子。然而，PVE后影响肝再生的因素尚不清楚。PVE后血浆VEGF水平显著升高，PVE后7天达到最高。PVE后血浆TGF-β水平也升高，并在14天达到峰值。PVE 7天后肝体积增加%与血浆VEGF水平显著相关。VEGF可影响PVE后肝剩余叶再生级联反应的激活。PVE后血浆VEGF水平的测量可能是潜在肝再生的预测因素，并可能为决定后续肝切除术的时间表提供有用的信息。

项目成果

Signal pathway of hepatic ischemia/reperfusion injury.

肝缺血/再灌注损伤的信号通路。

• 发表时间: 2005
• 期刊: Geka to Taisya/Eiyo 39
• 作者: Yoshidome H;Shimizu H;Kato A;Miyazaki M;et al.
• 通讯作者: et al.

Extended cold preservation of the graft liver enhances neutrophil-mediated pulmonary injury after liver transplantation.

• 发表时间: 2005-07
• 期刊: Hepato-gastroenterology
• 作者: H. Shimizu;M. Kataoka;M. Ohtsuka;Hiroshi Ito;F. Kimura;A. Togawa;H. Yoshidome;A. Kato;M. Miyazaki

Should the inferior vena cava be reconstructed after resection for malignant tumors?

• DOI: 10.1016/j.amjsurg.2005.01.010
• 发表时间: 2005-04-01
• 期刊: AMERICAN JOURNAL OF SURGERY
• 影响因子: 3
• 作者: Yoshidome, H;Takeuchi, D;Miyazaki, M
• 通讯作者: Miyazaki, M

Vascular endothelial growth factor and angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats

• DOI: 10.3748/wjg.v11.i46.7254
• 发表时间: 2005-12-14
• 期刊: WORLD JOURNAL OF GASTROENTEROLOGY
• 影响因子: 4.3
• 作者: Shimizu, Hiroaki;Mitsuhashi, Noboru;Miyazaki, Masaru
• 通讯作者: Miyazaki, Masaru

Increased plasma levels of IL-6 and IL-8 are associated surgical site infection after pancreaticoduodenectomy

胰十二指肠切除术后血浆 IL-6 和 IL-8 水平升高与手术部位感染相关

• 发表时间: 2006
• 期刊: Pancreas 32
• 作者: Kimura F;Shimizu H;Yoshidome H;Kato A;Miyazaki M;et al.
• 通讯作者: et al.