代谢相关脂肪性肝病（MAFLD）是一种与代谢紊乱密切相关的慢性肝病，其发病率在全球范围内不断上升，带来了沉重的卫生与经济负担。肝X受体（LXR）是核受体家族的重要成员，在脂质代谢稳态、炎症反应及组织纤维化等多种生理病理过程中发挥关键调控作用，其信号通路的失调与MAFLD的发病密切相关。单纯LXR调节剂虽在该领域具有治疗潜力，但仍面临脂代谢紊乱、肝脏脂肪变性加重等显著负面效应，严重限制了其临床转化。中医药具有多靶点、多途径、整体调节的特点，在激活或抑制双向调节LXR的同时，通过协同调控其他信号通路（如沉默信息调节因子1、腺苷酸活化蛋白激酶、核因子κB等）、诱导其下游靶基因（如固醇调节元件结合蛋白1C、三磷酸腺苷结合盒转运体等）选择性转录、对LXRα与LXRβ亚型的选择性调控、在不同类型组织细胞（如肝细胞、肠道细胞、Kupffer细胞等）中对LXR功能的选择性调节等方式，有效改善MAFLD病理状态，并避免单纯LXR激活或抑制的负面效应，具有良好的应用前景。对相关领域国内外研究进展进行总结，以期为后续基础探索与药物开发提供借鉴与参考。

Metabolic dysfunction-associated fatty liver disease (MAFLD), a chronic liver disease closely linked to metabolic disorders, has seen a rising global incidence, posing a substantial health and economic burden. The liver X receptor (LXR), a key member of the nuclear receptor family, plays a central regulatory role in physiological and pathological processes including lipid metabolism, inflammatory response, and tissue fibrosis. Dysregulation of the LXR signaling pathway is closely linked to the pathogenesis of MAFLD. While single LXR modulators exhibits therapeutic potential in this field, they can cause adverse effects such as lipid metabolism disorders and aggravated hepatic steatosis, severely limiting their clinical application. Traditional Chinese medicine (TCM) is characterized by multi-target, multi-pathway, and holistic regulatory mechanisms. While bidirectionally modulating LXR (through activation or inhibition), TCM can ameliorate MAFLD pathology and mitigate the adverse effects associated with singular LXR activation or inhibition. This is achieved through multiple mechanisms: synergistically regulating other signaling pathways (e.g., Sirtuin 1, AMP-activated protein kinase, nuclear factor kappa B); selectively inducing transcription of LXR downstream target genes (e.g., sterol regulatory element-binding protein 1C, ATP-binding cassette transporters); achieving subtype-selective regulation of LXRα and LXRβ; and exerting cell-type-selective modulation of LXR function across various tissues (e.g., hepatocytes, intestinal cells, Kupffer cells). Consequently, TCM shows great promise in the treatment of MAFLD. Based on these insights, this article reviews recent domestic and international research progress, aiming to provide a reference for future basic research and drug development.

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国家科技重大专项（2025ZD0551000）；国家自然科学基金项目（82305074）；全国名老中医药专家传承工作室建设项目（国中医药人教函[2022]75号）；仲景工程-第三批青苗人才-2024年中医扶持专项-第二批2109999（豫财社[2024]84号文中医扶持列2100601）；河南省中医药科研专项课题（2025ZY1011）