Inflammation-Associated Lipid Mediators in Cholestatic Hepatobiliary Diseases and Effect of PAF-AH

胆汁淤积性肝胆疾病中炎症相关脂质介质及 PAF-AH 的作用

• 批准号: 12670456
• 负责人: SHODA Junichi
• 金额: $ 2.56万
• 依托单位: THE UNIVERSITY OF TSUKUBA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670456/
• 关键词: bilirubin; obstractive cholestasis; primary hepatolithiasis; hepatobiliary malignancy; biliary secretory mechanism; canalicular membrane transporter; bile acid; oxidative stress; 経皮経肝胆道ドレナージ; 輸送蛋白; 胆汁うっ滞; 脂質メディエーター; 炎症病態; ホスホリパーゼAz; 血小板活性化因子

The transport of biliary constituents across the canalicular membrane is the rate-limiting step in bile formation. Since long-standing biliary obstruction and complication of cholangitis associated with biliary infection have a large influence upon the hepatic secretory function through inflammation-related oxidative stress on the liver, interest should be focused on the expression levels of canalicular membrane transporter proteins in the cholestatic liver of patients with hepatobiliary diseases. We determined the molecular and immunohistochemical expression of canalicular transporter proteins, for bilirubin conjugate and bile acid,in the liver of patients with hepatolithiasis and in those of the patients with obstructive cholestasis who had undergone preoperative biliary drainage. Furthermore, their expression levels were correlated with the impairment of biliary secretion.This study concludes that in the liver of hepatobiliary diseases, the altered expression of the canalicular transporters may be associated with the impairment of bile formation and secretion, propably through inflammation-related oxidative stress on the liver.

胆汁成分穿过小管膜的转运是胆汁形成的限速步骤。由于长期的胆道梗阻和胆道感染相关的胆管炎并发症通过炎症相关的氧化应激对肝脏分泌功能有很大的影响，因此应该关注肝胆疾病患者胆汁淤积性肝脏中小管膜转运蛋白的表达水平。我们测定了肝内胆管结石患者和接受术前胆道引流的梗阻性胆汁淤积患者肝脏中胆红素结合物和胆汁酸小管转运蛋白的分子和免疫组化表达。此外，他们的表达水平与损害的胆汁secrety.This研究的结论是，在肝脏的肝胆疾病，小管转运蛋白的表达改变可能与损害胆汁的形成和分泌，可能通过炎症相关的氧化应激对肝脏。

项目成果

Asano, T., Shoda, J., et al.: "Expression of cyclooxygenase-2 in carcinoma of the gallbladder-crucial role of arachidonate metabolism in tumor growth and progression"Clin Cancer Res. 8. 1157-1167 (2002)

Asano, T., Shoda, J.等人：“胆囊癌中环氧合酶-2的表达——花生四烯酸代谢在肿瘤生长和进展中的关键作用”Clin Cancer Res。

Shoda, J., Oda, K., Suzuki, H., Sugiyama, Y., Ito., K, Cohen, D.E., Feng, L., Kamiya, Nimura, Y., Miyazaki, H., Kano, M., Matsuzaki, Y., Tanaka, N.: "Metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic

Shoda, J.、Oda, K.、Suzuki, H.、Sugiyama, Y.、Ito., K、Cohen, D.E.、Feng, L.、Kamiya, Nimura, Y.、Miyazaki, H.、Kano, M.

Shoda,J. et al.: "Metabolic defects of cholesterol, phospholipid, and bile acid in the liver of patients with intrahepatic calculi, and etiological significance"Hepatology. (In press). (2001)

绍达，J.

Shoda, J., et al.: "The molecular basis of gallstone pathogenesis and its potential therapy Hepatolithiasis-Epidemiology and pathogenesis update"Frontiers in Bioscience. 8. 398-409 (2003)

Shoda, J. 等人：“胆结石发病机制的分子基础及其潜在疗法肝石症 - 流行病学和发病机制更新”生物科学前沿。

Itoh, S. et al.: "Suppression of hepatic lesions in a murine graft-versus-host reaction by antibodies against adhesion molecules"Journal of Hepatology. 32. 587-595 (2000)

Itoh, S. 等人：“通过抗粘附分子的抗体抑制小鼠移植物抗宿主反应中的肝脏病变”《肝脏病学杂志》。