外周时钟基因在非酒精性脂肪性肝炎发展与防治中的作用

刘思言; 田静怡; 黄雨扬; 谷天麒; 邓茗月; 杨攀

doi:10.12449/JCH241222

外周时钟基因在非酒精性脂肪性肝炎发展与防治中的作用

DOI: 10.12449/JCH241222

1.
重庆医科大学国际医学院，重庆 401331
2.
重庆医科大学附属第二医院急救部，重庆 400000

基金项目:

重庆市自然科学基金 (cstc2020jcyj-bshX0068);

2021年重庆市中青年高端人才项目 (yxgdrc20210101);

2022年国家级创新训练项目 (202210631001)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：刘思言负责设计论文框架，查找文献，起草论文；田静怡负责查找文献，绘制图表及文章撰写；黄雨扬、谷天麒、邓茗月负责文章撰写和修改；杨攀负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
杨攀， tmmu_yp@126.com （ORCID： 0000-0003-3962-6281）

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出版历程
- 收稿日期: 2024-04-07
- 录用日期: 2024-05-23
- 出版日期: 2024-12-25

Role of peripheral clock genes in the progression， prevention， and treatment of nonalcoholic steatohepatitis

1.
International Medical College，Chongqing Medical University，Chongqing 401331，China
2.
Emergency Department，The Second Affiliated Hospital of Chongqing Medical University，Chongqing 400000，China

Research funding:

Natural Science Foundation of Chongqing (cstc2020jcyj-bshX0068);

2021 Chongqing Municipal Middle and Young Age High-end Talent Project (yxgdrc20210101);

2022 National Level Innovation Training Project (202210631001)

More Information

Corresponding author: YANG Pan， tmmu_yp@126.com （ORCID： 0000-0003-3962-6281）

摘要

摘要: 非酒精性脂肪性肝炎（NASH）作为非酒精性脂肪性肝病的严重临床表现形式，以肝脂质沉积、炎症损伤为特征。目前NASH的临床治疗药物仍处于探索实验阶段，亟待取得进展。有研究指出NASH的发病机制与肝脏昼夜节律紊乱有关，具体可表现为肝时钟基因如BMAL1等表达失调，导致肝内脂质生成增多、脂肪酸氧化减少以及促炎症因子激活。因此，改善肝脏昼夜节律，调节肝时钟基因表达被视为防治NASH的可行策略。目前已有通过激活时钟基因编码蛋白治疗NASH的药物应用于动物实验，如REVERB全激动剂SR9009，其能抑制肝脏的炎症发展，有效证实了靶向时钟编码蛋白在NASH治疗中的可能性。本文总结了肝时钟基因在调节肝脂质代谢与炎症发生发展中的作用，阐述了近年来以时钟基因及其相关蛋白作为靶点的药物研究进展，以期为NASH治疗提供新靶点。
- 非酒精性脂肪性肝病 /
- 昼夜节律 /
- 时钟蛋白质类
Abstract: As a severe clinical manifestation of nonalcoholic fatty liver disease， nonalcoholic steatohepatitis （NASH） is characterized by lipid deposition and inflammatory damage in the liver. At present， clinical medications for NASH are still in the exploratory phase， and it is urgent to make progress. Recent studies have shown that the pathogenesis of NASH is associated with circadian rhythm disorders in the liver， with the specific manifestation of dysregulated expression of liver clock genes such as BMAL1， which increases hepatic lipogenesis， reduces fatty acid oxidation， and activates pro-inflammatory factors. Therefore， improving circadian rhythm of the liver and regulating the expression of liver clock genes are feasible strategies for the prevention and treatment of NASH. Currently， some medications for NASH via activating the proteins encoded by clock genes have been applied in animal experiments， for example， the REVERB full-agonist SR9009 can inhibit the development of liver inflammation， which confirms the possibility of NASH treatment by targeting the proteins encoded by clock genes. This article summarizes the role of hepatic clock genes in regulating lipid metabolism and the development and progression of inflammation in the liver and elaborates on the recent advances in medications targeting clock genes and the proteins encoded by clock genes， in order to provide new targets for the treatment of NASH.
- Non-alcoholic Fatty Liver Disease /
- Circadian Rhythm /
- CLOCK Proteins

HTML全文

图 1 分子钟组成（转录-翻译反馈调节环路）

Figure 1. Contents of molecular clock （transcription-translation feedback loop）

下载: 全尺寸图片幻灯片

图 2 时钟基因及其相关蛋白参与调节肝脂质平衡的机制

Figure 2. The roles of clock genes and proteins in lipid homeostasis of liver

下载: 全尺寸图片幻灯片

图 3 时钟基因及其相关蛋白参与NASH炎症发生、发展的机制

Figure 3. The roles of clock genes and proteins in inflammation progression of liver

下载: 全尺寸图片幻灯片

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