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胆道疾病的营养因素(营养方面):胆石病和胰胆管合流异常中的胆汁酸和脂质代谢。

Nutritional factors (nutritional aspects) in biliary disorders: bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction.

机构信息

Programs of Applied Medicine, Clinical Pharmacotherapy, Department of General Internal Medicine, Hiroshima University Hospital, Graduate School of Medical Science, Hiroshima, Japan.

出版信息

J Gastroenterol Hepatol. 2013 Dec;28 Suppl 4:103-7. doi: 10.1111/jgh.12241.

Abstract

Nutritional factors play a key role in the pathogenesis of biliary diseases such as gallstones and pancreaticobiliary maljunction. Gallstones are primarily classified into cholesterol stone and pigment stone according to the major composition. Cholesterol gallstone formation is very likely based upon supersaturated bile formation, and pigment stones are formed in bile rich in bilirubin. Thus, defects of hepatic metabolism of lipids and organic anions lead to biliary stones. Here, the recent understanding of cholesterol gallstone pathogenesis is elaborated. On the other hand, there is another important link of biliary lipid degradation to serious biliary disease, namely pancreaticobiliary maljunction. Lysophosphatidylcholine (lysoPC), a derivative of phosphatidylcholine hydrolysis by phospholipase A2, is a highly abundant bioactive lipid mediator present in circulation as well as in bile. Increases in bile of lysoPC and phospholipase A2 have been reported in pancreaticobiliary maljunction and considered to be the major risk factor for biliary tract cancers. Further, oxidized fatty acids have been established as a potent ligand for G2A, a member of G protein-coupled receptor family that mediates a diverse array of biological processes including cell growth and apoptosis. Thus, both of lysoPC and free fatty acids are supposed to play an important role through G2A in biliary inflammation and carcinogenesis of pancreaticobiliary maljunction. Taken together, nutritional factors, especially lipid compounds, are seemingly crucial in the pathogenesis of biliary diseases, and such a causal relationship is reviewed by mainly authors' previous publications.

摘要

营养因素在胆病(如胆结石和胰胆管合流异常)的发病机制中起着关键作用。胆结石主要根据主要成分分为胆固醇结石和色素结石。胆固醇结石的形成极有可能基于胆汁的过饱和形成,而色素结石则形成于富含胆红素的胆汁中。因此,肝脏脂质和有机阴离子代谢的缺陷导致胆石形成。这里详细阐述了胆固醇胆结石发病机制的最新认识。另一方面,胆汁脂质降解与严重胆病之间还有另一个重要联系,即胰胆管合流异常。溶血磷脂酰胆碱(lysoPC)是磷脂酶 A2 水解磷脂酰胆碱的衍生物,是一种在循环中和胆汁中都存在的高度丰富的生物活性脂质介质。据报道,胰胆管合流异常时胆汁中的 lysoPC 和磷脂酶 A2 增加,并被认为是胆道癌的主要危险因素。此外,氧化脂肪酸已被确立为 G 蛋白偶联受体家族成员 G2A 的有效配体,G2A 介导包括细胞生长和凋亡在内的多种生物学过程。因此,lysoPC 和游离脂肪酸都通过 G2A 参与胰胆管合流异常的胆道炎症和癌变,发挥重要作用。综上所述,营养因素,尤其是脂质化合物,在胆病的发病机制中似乎起着至关重要的作用,主要作者的先前出版物综述了这种因果关系。

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