Analysis of the role of hepatic remodeling and signal of hepatic regeneration after hepatic ischemia/reperfusion injury in obstructive jaundice

梗阻性黄疸肝缺血/再灌注损伤后肝重塑及肝再生信号的作用分析

• 批准号: 20591621
• 负责人: KATO Atsushi
• 金额: $ 3万
• 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591621/
• 关键词: 閉塞性黄疸; 阻血再灌流; 肝再生; 転写因子; 肝星細胞

Cholestasis of the liver is known to be an important risk factor for surgical morbidity and mortality after major hepatectomy. However, the mechanism of liver injury in cholestatic liver is not fully understood. Our data suggests that hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver. To identify predictive factors for postoperative liver regeneration after major hepatectoy, clinical factors and liver volumetric changes determined by CT volumetry and CT attenuation values (CT-AVs) were compared in patients with and without postoperative hepatic failure. Postoperative lower CT-AV was the only independent risk factor of postoperative hepatic failure. 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. Plasma VEGF levels were increased markedly after PVE and were maximal after 7 days of 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.

肝胆汁淤积是肝切除术后手术发病率和死亡率的重要危险因素。然而，胆汁淤积性肝损伤的机制还不完全清楚。我们的数据表明，肝星状细胞活化和内皮素-1的产生增加在胆汁淤积性肝脏缺血/再灌注损伤中起着至关重要的作用。为了确定主要肝切除术后肝再生的预测因素，比较了有和无术后肝功能衰竭患者的临床因素和CT容积测定法和CT衰减值（CT-AV）测定的肝脏体积变化。术后CT-AV降低是术后肝功能衰竭的唯一独立危险因素。术前门静脉栓塞（PVE）是一种有效的手段，创造未来的剩余肝脏肥大，从而导致广泛的肝切除术治疗肝脏恶性肿瘤的安全性。PVE后血浆VEGF水平显著升高，PVE后7天达到最高。PVE后血浆VEGF水平的测量可能是一个潜在的肝再生的预测因素，并可能提供有用的信息，以决定后续肝切除术的时间表。

项目成果

Aggressive Surgical Resection for Hilar Cholangiocarcinoma of the Left-Side Predominance Radicality and Safety of Left-Sided Hepatectomy

• DOI: 10.1097/sla.0b013e3181be0085
• 发表时间: 2010-02-01
• 期刊: ANNALS OF SURGERY
• 影响因子: 9
• 作者: Shimizu, Hiroaki;Kimura, Fumio;Miyazaki, Masaru
• 通讯作者: Miyazaki, Masaru

Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver.

• DOI: 10.3164/jcbn.10-74
• 发表时间: 2011-03
• 期刊: Journal of clinical biochemistry and nutrition
• 影响因子: 2.4
• 作者: Suzuki T;Yoshidome H;Kimura F;Shimizu H;Ohtsuka M;Takeuchi D;Kato A;Furukawa K;Yoshitomi H;Iida A;Dochi T;Miyazaki M
• 通讯作者: Miyazaki M

Endothelin-1 aggravates hepatic ischemia/reperfusion injury duringobstructive cholestasis in bile duct ligated mice.

Endothelin-1 会加重胆管结扎小鼠阻塞性胆汁淤积期间的肝脏缺血/再灌注损伤。

• 发表时间: 2010
• 期刊: Journal of Surgical Research
• 影响因子: 2.2
• 作者: Hiroyuki Nagai;Atsushi Kato;Fumio Kimura;Hiroaki Shimizu;Hiroyuki Yoshidome;et al.
• 通讯作者: et al.

Mechanism of neutrophil accumulation in sinusids after extrahepatic biliry obstruction.

肝外胆道梗阻后窦窦中性粒细胞积聚的机制。

• 发表时间: 2008
• 期刊: Hapetogastroenterology 55
• 作者: Wakabayashi Y;Shimizu H;Kimura F;Yoshidome H;Ohtsuka M;Kato A;Miyazaki M
• 通讯作者: Miyazaki M

Interleukin-18 Exacerbates Pulmonary Injury after Hepatic Ischemia/Reperfusion in Mice

• DOI: 10.1016/j.jss.2008.08.009
• 发表时间: 2010-01-01
• 期刊: JOURNAL OF SURGICAL RESEARCH
• 影响因子: 2.2
• 作者: Takeuchi, Dan;Yoshidome, Hiroyuki;Miyazaki, Masaru
• 通讯作者: Miyazaki, Masaru