固醇调节元件结合蛋白（SREBP）在非酒精性脂肪性肝病中的作用机制及治疗靶点

李安琪; 赵佩然; 赵玉强; 王锐; 杨婧

doi:10.12449/JCH240726

固醇调节元件结合蛋白（SREBP）在非酒精性脂肪性肝病中的作用机制及治疗靶点

DOI: 10.12449/JCH240726

李安琪¹,
赵佩然¹,
赵玉强¹,
王锐²,
杨婧^1, , ,

1.
黑龙江中医药大学基础医学院，哈尔滨 150040
2.
黑龙江中医药大学药学院，哈尔滨 150040

基金项目:

国家自然科学基金 (81603418);

黑龙江省优秀青年人才项目 (2020YQ05)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：李安琪负责课题设计，资料分析，撰写论文；王锐负责修改论文；赵玉强、赵佩然参与收集及分析文献资料；杨婧负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
杨婧， yangjingdx@sina.com （ORCID： 0000-0003-4770-3515）

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出版历程
- 收稿日期: 2023-10-23
- 录用日期: 2023-11-29
- 出版日期: 2024-07-25

Mechanism of action of sterol regulatory element-binding proteins in nonalcoholic fatty liver disease and related therapeutic targets

1.
College of Basic Medical Heilongjiang University of Chinese Medicine，Harbin 150040，China
2.
College of Pharmacy Heilongjiang University of Chinese Medicine，Harbin 150040，China

Research funding:

National Natural Science Foundation of China (81603418);

Heilongjiang Province Excellent Young Talents Program (2020YQ05)

More Information

Corresponding author: YANG Jing， yangjingdx@sina.com （ORCID： 0000-0003-4770-3515）

摘要

摘要: 非酒精性脂肪性肝病（NAFLD）已成为全球范围内最常见的肝脏疾病，是肝癌发展的重要风险因素。然而，NAFLD的发病机制目前仍未被完全阐明，且尚无特异性的有效治疗措施。固醇调节元件结合蛋白（SREBP）是一类重要的核转录因子，主要通过激活胆固醇、脂肪酸和甘油三酯合成及摄取的相关基因来维持体内脂质代谢的平衡，是治疗代谢性疾病的靶点。本文对SREBP参与NAFLD发病机制的最新进展以及SREBP靶向治疗NAFLD的最新证据进行综述。值得注意的是，最近研究发现SREBP抑制与自噬受损共同引发肝损伤。因此，过度抑制脂肪生成对NAFLD的治疗可能起反作用。总体而言，SREBP是一个具有广阔前景的NAFLD治疗靶点，其对脂质代谢的分子机制受多种因素的调控，而这些因素正在被深入探索和分析，对NAFLD治疗具有重要的临床意义。
- 非酒精性脂肪性肝病 /
- 胆固醇调节元件结合蛋白质类 /
- 脂肪生成 /
- 炎症 /
- 纤维化
Abstract: Nonalcoholic fatty liver disease （NAFLD） has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma. However， the pathogenesis of NAFLD remains unclear， and there is still a lack of specific treatment measures. Sterol regulatory element-binding proteins （SREBP） are an important nuclear transcription factor， which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol， fatty acids， and triglycerides， and therefore， SREBP are a target for the treatment of metabolic diseases. This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD. It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage. Therefore， excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD. In conclusion， SREBP is a promising therapeutic target for NAFLD； the molecular mechanism of SREBP in lipid metabolism is regulated by many factors， and these factors are being deeply explored and analyzed， which has an important clinical significance for the treatment of NAFLD.
- Non-alcoholic Fatty Liver Disease /
- Sterol Regulatory Element Binding Proteins /
- Lipogenesis /
- Inflammation /
- Fibrosis

HTML全文

图 1 SREBP的激活机制

注： GP78，E3泛素蛋白连接酶AMFR；Ub，泛素；PUFA，多不饱和脂肪酸。

Figure 1. Activation mechanism of SREBP

下载: 全尺寸图片幻灯片

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