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原发性胆汁性胆管炎和原发性硬化性胆管炎中的顶端钠依赖性转运体抑制剂

Apical Sodium-Dependent Transporter Inhibitors in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.

作者信息

Hegade Vinod S, Jones David E J, Hirschfield Gideon M

机构信息

Institute of Cellular Medicine, NIHR Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK.

出版信息

Dig Dis. 2017;35(3):267-274. doi: 10.1159/000450988. Epub 2017 Mar 1.

Abstract

Bile acids (BAs) have gained mainstream attention since the discovery of their key role as signalling molecules in health and disease. The apical sodium-dependent transporter (ASBT) protein located in the terminal ileum plays an important physiological role in the enterohepatic circulation of BAs and therefore essential for the BA homeostasis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the 2 most common cholestatic liver diseases are characterised by altered BA flow and BA composition, which contribute to disease progression and symptom (pruritus) development. Therefore, changing the circulating BA pool in patients with PBC and PSC may have therapeutic implications. To this end, pharmacological inhibition of ASBT is fast emerging as an interesting target. In this review, we discuss the recent evidence for potential therapeutic use of ASBT inhibitors to treat PBC and PSC patients.

摘要

自发现胆汁酸(BAs)作为健康和疾病中的信号分子发挥关键作用以来,它们已受到主流关注。位于回肠末端的顶端钠依赖性转运体(ASBT)蛋白在胆汁酸的肠肝循环中发挥重要生理作用,因此对胆汁酸稳态至关重要。原发性胆汁性胆管炎(PBC)和原发性硬化性胆管炎(PSC)是两种最常见的胆汁淤积性肝病,其特征是胆汁酸流动和胆汁酸组成改变,这有助于疾病进展和症状(瘙痒)发展。因此,改变PBC和PSC患者的循环胆汁酸池可能具有治疗意义。为此,对ASBT的药理抑制正迅速成为一个有趣的靶点。在本综述中,我们讨论了ASBT抑制剂用于治疗PBC和PSC患者的潜在治疗用途的最新证据。

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