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孤儿受体调控慢性肝病的研究进展

杨智荟¹, 王佳慧¹, 汪磊¹, 段雪琳², 王鸿红¹, 彭岳², 赵铁建², 郑洋^1,*

¹广西中医药大学赛恩斯新医药学院医学系，南宁 530222；²广西中医药大学基础医学院生理教研室，南宁 530222

摘要

脂肪堆积过多、生物钟失调、病毒感染、持续炎症反应等可造成肝脏炎症、纤维化、癌变，促进慢性肝病的发展。深入了解导致慢性肝病的病因，以及影响其发生和发展的基本机制，有助于确定潜在的治疗目标，进行靶向治疗。孤儿受体(orphan nuclear receptors, ONRs)是指无相应内源性配体与其结合的受体，对ONRs及其生物学特性的研究促进了合成配体的发展，对研究治疗多种疾病的有效靶点具有重要作用。近年来，研究发现ONRs对于维持正常的肝脏功能至关重要，其功能障碍可影响各种肝脏疾病。ONRs可通过调控激素、转录因子，影响生物钟、氧化应激等方式，影响肝脏脂质代谢、炎症反应、癌细胞增殖等病理生理学活动。基于此，本文重点介绍维甲酸相关孤儿受体(retinoid related orphan nuclear receptors, RORs)亚家族、孕烷X受体(pregnane X receptor, PXR)、白细胞衍生的趋化因子2 (leukocyte cell derived chemotaxin 2, LECT2)、核受体Nur77、肝细胞核因子4α (hepatocyte nuclear factor 4α, HNF4α)这些ONRs通过不同的方式调控不同类型慢性肝病的发生和发展，为基于ONRs调控慢性肝病治疗策略提供有益参考。

关键词： 孤儿受体; RORs; LECT2; Nur77; 慢性肝病

Research progress of the regulation of orphan nuclear receptors on chronic liver diseases

YANG Zhi-Hui¹, WANG Jia-Hui¹, WANG Lei¹, DUAN Xue-Lin², WANG Hong-Hong¹, PENG Yue², ZHAO Tie-Jian², ZHENG Yang^1,*

¹Department of Medicine, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning 530222, China；²Department of Physiology, School of Basic Medicine, Guangxi University of Chinese Medicine, Nanning 530222, China

Abstract

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

Key words: orphan nuclear receptors; RORs; LECT2; Nur77; chronic liver diseases

收稿日期：　　录用日期：

通讯作者：郑洋　　E-mail: zhengy@gxtcmu.edu.cn; 1793853705@qq.com

引用本文：

杨智荟, 王佳慧, 汪磊, 段雪琳, 王鸿红, 彭岳, 赵铁建, 郑洋. 孤儿受体调控慢性肝病的研究进展[J]. 生理学报 2023; 75 (4): 555-568.

YANG Zhi-Hui, WANG Jia-Hui, WANG Lei, DUAN Xue-Lin, WANG Hong-Hong, PENG Yue, ZHAO Tie-Jian, ZHENG Yang. Research progress of the regulation of orphan nuclear receptors on chronic liver diseases. Acta Physiol Sin 2023; 75 (4): 555-568 (in Chinese with English abstract).