Pathogenetic Mechanism for Hypersecretion of Mucin Glycoprotein in Cholelithiasis

胆石症粘蛋白糖蛋白分泌过多的发病机制

• 批准号: 09670509
• 负责人: SHODA Junichi
• 金额: $ 2.05万
• 依托单位: 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670509/
• 关键词: cholelithiasis; mucin; arachidonate metabolism; phospholipase AィイD22ィエD2; mucin gene; 肝内結石症; ムチンコア蛋白遺伝子; 胆管炎; 結石成因; ホスホリパーゼA_2受容体; CFTR; 難治性疾患; 硫酸ムチン

Multiple cholesterol stones are associated with more biliary complications and exhibit more rapid cholesterol nucleation than solitary stones. Secretory or group II phospholipase AィイD22ィエD2 (PLAィイD22ィエD2-II) levels in gallbladder bile were significantly higher in patients with multiple cholesterol stones than in those with solitary stones or control subjects. Increased biliary PLAィイD22ィエD2-II levels in multiple cholesterol stones were associated with a concomitant increase in the protein and hexosamine concentrations as well as gallbladder bile viscosity. Increased PLAィイD22ィエD2-II in gallbladder bile may be of pathogenetic importance in patients with multiple cholesterol stones, probably through potentiating gallbladder mucosal inflammation with associated biliary alterations favoring cholesterol crystal formation.Ursodeoxycholate (UDC) decreases biliary levels of various pronucleating proteins, possibly due to its membrane-protective effects on the inflamed gallbladder mucosa. Long-te … More rm UDC administration was observed to lower the increased PLAィイD22ィエD2-II protein mass and mRNA level as well as the PLAィイD22ィエD2-V mRNA level in the gallbladders of patients with multiple cholesterol stones, which in turn may be of therapeutic importance in improving the gallbladder mucosal inflammation. Effects of UDC on secretory low molecular weight PLAィイD22ィエD2s as inflammatory mediators may relate to the reported efficacy of UDC treatment in cholesterol gallstone disease.Intrahepatic calculi is characterized by an intractable course and frequent recurrences. Chronic proliferative cholangitis may underlie the complex nature of the disease. PLAィイD22ィエD2-II levels were significantly higher in the bile from the stone-containing hepatic ducts than in the ductal bile from gallbladder stone patients. The increased sPLAィイD22ィエD2 levels were associated with a concomitant increase in prostaglandin EィイD22ィエD2 and total mucin concentrations. The affected bile ducts showed an increased mRNA level of PLAィイD22ィエD2-II compared with the ducts from control subjects. In intrahepatic calculi, an enhanced expression of the PLAィイD22ィエD2-II may be of pathophysiological significance for the chronic proliferative cholangitis, probably through biliary alterations favoring growth of preexisting stones and even further progressions. Less

多发性胆固醇结石与更多的胆道并发症相关，并且比孤立性结石表现出更快的胆固醇成核。多发性胆固醇结石患者胆囊胆汁中分泌型或II型磷脂酶A β D22 β D2（PLA β D22 β D2-II）水平显著高于单发性结石患者或对照组。多发性胆固醇结石患者胆汁中聚乳酸脱氢酶D22脱氢酶D2-II水平的增加与蛋白质和氨基己糖浓度以及胆囊胆汁粘度的同时增加有关。胆囊胆汁中PLA-D22-D2-II的增加可能在多发性胆固醇结石患者中具有重要的发病意义，可能是通过增强胆囊粘膜炎症以及相关的有利于胆固醇晶体形成的胆汁改变。熊去氧胆酸盐（UDC）降低胆汁中各种原核蛋白的水平，可能是由于其对发炎的胆囊粘膜的膜保护作用。龙德 ...更多信息 rm UDC给药可降低多发性胆固醇结石患者胆囊中增加的PLA受体D22亚型D2-II蛋白质质量和mRNA水平以及PLA受体D22亚型D2-V mRNA水平，这反过来可能对改善胆囊粘膜炎症具有治疗意义。UDC对作为炎症介质的分泌型低分子量PLA β-D22 β-D2 s的影响可能与UDC治疗胆固醇结石病的疗效有关。肝内结石的特点是难治性和经常复发。慢性增生性胆管炎可能是疾病复杂性的基础。含石肝管胆汁中PLA受体D22受体D2-II水平显著高于胆囊结石患者胆管胆汁中PLA受体D22受体D2-II水平。sPLA β-D22 β-D2水平的增加与前列腺素E β-D22 β-D2和总粘蛋白浓度的伴随增加相关。与对照组相比，受影响的胆管显示PLA受体D22受体D2-II的mRNA水平增加。在肝内结石中，PLA β D22 β D2-II表达增强可能对慢性增生性胆管炎具有病理生理学意义，可能是通过胆管改变促进既存结石的生长甚至进一步进展。少

项目成果

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Shoda J：“高脂蛋白血症中血浆甲羟戊酸和 7α-羟基-4-胆固醇-3-酮水平的同时测定”《肝病学》25. 18-26 (1997)。

Kano, M., Shoda, J., Irimura, T., Ueda, T., Iwasaki, R., Urasaki, T., Kawauchi, Y., Asano, T., Matsuzaki, Y., Tanaka, N.: "Effects of long-term ursodeoxycholate administration on expression levels of secretory low molecular weight phospholipase AィイD22ィエD2

Kano, M.、Shoda, J.、Irimura, T.、Ueda, T.、Iwasaki, R.、Urasaki, T.、Kawauchi, Y.、Asano, T.、Matsuzaki, Y.、Tanaka, N.： “长期给予熊去氧胆酸对分泌型低分子量磷脂酶 A-D22-D2 表达水平的影响

Tomida S.et al.: "Long-term ursodeoxycholic acid therapy is〜"Hepatology. 30. 6-13 (1999)

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Shoda J,et al.: "Secretory low-molecular-weight phospholipase A2 and their specific receptor in bile ducts of patients with intrahepatic calculi: factors of chronic proliferative cholalngitis" Hepatology. 29(in press). (1999)

Shoda J等人：“肝内结石患者胆管中的分泌性低分子量磷脂酶A2及其特异性受体：慢性增殖性胆管炎的因素”肝病学。

Ikegami T.et al.: "The chemopreventive role of ursodeoxycholic acid〜"Cancer Letter. 134. 129-139 (1999)

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