《生命科学》 2026, 38(8): 1429-1445
从硒代谢到肝病干预：硒蛋白的合成、功能与分子机制
摘 要：
硒是人体必需微量元素中的关键一员，其相关研究已深入分子层面，涵盖了硒的体内代谢途径、硒蛋白的生物合成及其在调控氧化应激、免疫炎症与代谢适应等重要生理过程中的功能。肝脏作为机体代谢与免疫调节的核心器官，是全身物质与能量代谢的枢纽，也是硒代谢和硒蛋白表达的关键场所。大量证据表明，硒通过其特有的硒蛋白，在维持肝脏正常生理功能中扮演不可或缺的角色。本文拟从硒的体内代谢过程出发，系统阐述硒蛋白的合成机制、主要生物学功能，并重点探讨其在代谢功能障碍相关脂肪性肝病、病毒性肝炎、肝纤维化及肝癌等多种肝脏疾病发生发展中的作用与潜在机制，以期为硒与肝脏健康的深入研究提供理论参考与新的思路。
通讯作者：丁秋蓉 , Email:qrding@sinh.ac.cn
Abstract:
Selenium (Se), an essential trace element, has attracted increasing research interest as the vital role of micronutrients in human physiology becomes ever more apparent. Its biological functions are primarily mediated through selenoproteins, in which selenium is incorporated as the 21st amino acid selenocysteine (Sec), forming the active center. These proteins are indispensable for regulating key processes such as oxidative stress, immune-inflammatory responses, and metabolic homeostasis. The liver, a central organ governing both metabolism and immunity, serves as a hub for systemic energy and material exchange and is the primary site for selenium metabolism and selenoprotein expression. Accumulating evidence underscores that selenium status is closely linked to normal liver function. This review systematically explores the intricate relationship between selenium and liver health. We begin by summarizing the dietary sources and metabolic dynamics of selenium in vivo, along with recent advances in novel selenium intervention strategies. A key focus is the unique biosynthesis of selenoproteins, particularly the sophisticated UGA recoding mechanism that enables the precise incorporation of Sec into polypeptide chains. We also discuss the hierarchical regulation of selenoprotein synthesis, a crucial adaptive strategy that prioritizes essential physiological functions during fluctuations in selenium availability. Furthermore, this article provides a comprehensive overview of the multifaceted roles that major selenoproteins play in maintaining liver homeostasis. We examine their involvement and potential mechanisms in the pathogenesis and progression of various liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). By evaluating both the potential benefits and limitations of selenium upplementation in clinical practice, we address the challenge posed by its complex “U-shaped” dose-response relationship, which complicates therapeutic application. Finally, we offer perspectives on future research directions, highlighting the need for personalized and precisely targeted nutritional strategies. This review aims to provide a theoretical foundation and novel insights that bridge the gap between molecular research and the clinical application of selenium in liver health and disease.
Communication Author：DING Qiu-Rong , Email:qrding@sinh.ac.cn
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