微环境不同组分动态变化调控肝纤维化发展的特征与机制

赵慧兰; 刘宗绪; 李淑敏; 王之枫; 刘明慧; 盛倩; 柯坤彬; 石西南

doi:10.12449/JCH250423

微环境不同组分动态变化调控肝纤维化发展的特征与机制

DOI: 10.12449/JCH250423

赵慧兰¹,
刘宗绪¹,
李淑敏¹,
王之枫¹,
刘明慧¹,
盛倩¹,
柯坤彬²,
石西南^{1, 3, , ,}

1.
云南中医药大学中药学院，昆明 650500
2.
昆明医科大学第一附属医院泌尿外科，昆明 650000
3.
云南中医药大学中药学院暨云南省南药可持续利用研究重点实验室，昆明 650500

基金项目:

国家自然科学基金 (82060862);

云南省科技厅-云南中医药大学联合重点项目 (202101AZ070001-003);

云南省科技厅应用基础项目 (202301AT070098)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：赵慧兰负责撰写、修改文章；刘宗绪、王之枫、李淑敏、刘明慧、盛倩负责论文查新及校对；石西南、柯坤彬拟定写作思路及修改文章。

详细信息

通信作者:
石西南， 17387105981@163.com （ORCID： 0000-0002-8454-1845）

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- 被引次数: 0
出版历程
- 收稿日期: 2024-07-16
- 录用日期: 2024-10-30
- 出版日期: 2025-04-25

The characteristics and mechanism of dynamic changes of different components in microenvironment in regulating the progression of liver fibrosis

1.
College of Traditional Chinese Medicine，Yunnan University of Chinese Medicine，Kunming 650500，China
2.
Department of Urology，The First Affiliated Hospital of Kunming Medical University，Kunming 650000，China
3.
Key Laboratory of Sustainable Utilization of Yunnan Medicines，College of Traditional Chinese Medicine，Yunnan University of Chinese Medicine，Kunming 650500，China

Research funding:

National Natural Science Foundation of China (82060862);

Yunnan Provincial Science and Technology Department-Applied Basic Research Joint Special Funds of Chinese Medicine (202101AZ070001-003);

Yunnan Applied Basic Research Program (202301AT070098)

More Information

Corresponding author: SHI Xinan， 17387105981@163.com （ORCID： 0000-0002-8454-1845）

摘要

摘要: 肝脏有代谢、解毒、免疫防御等功能，肝脏微环境稳态的维持对机体健康极其重要。肝脏的微环境包括肝实质细胞、非实质细胞及非细胞成分等。不同病因导致肝脏慢性损伤性炎症反应，促进肝纤维化的形成和发展。在肝纤维化早、中晚不同时期的动态发展过程中，肝脏微环境的各种成分会发生一系列的变化，而这些能促进肝纤维化的恶性发展。深入探索微环境各成分变化机制对肝纤维化的发生机制和探索潜在的治疗策略至关重要。
- 细胞微环境 /
- 肝纤维化 /
- 肝星状细胞 /
- 枯否细胞 /
- 肝窦内皮细胞
Abstract: The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.
- Cellular Microenvironment /
- Hepatic Fibrosis /
- Hepatic Stellate Cells /
- Kupffer Cells /
- Liver Sinusoidal Endothelial Cells

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图 1 肝纤维化不同时期肝脏微环境各成分变化

Figure 1. Changes in components of the liver microenvironment at different stages of liver fibrosis

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表 1 肝纤维化不同时期肝脏微环境各成分变化对比

Table 1. Comparison of changes in components of the liver microenvironment across different stages of liver fibrosis

类别	微环境成分	肝纤维化早期	肝纤维化中晚期
肝实质细胞	肝细胞	肝细胞的损伤和死亡	肝细胞大量损伤并再生，聚集形成假小叶性细胞结节，压迫血管促进门静脉高压的发生
肝非实质细胞	HSC	活化并增殖，形态上仍保留一定的规则性	大量激活并向成纤维样细胞转化，形态不规则，数量增加形成纤维间隔
	Kupffer细胞	活化并释放TNF-α和IL-1等促炎因子，刺激HSC的激活	进一步活化，释放更多的促炎因子和趋化因子如PDGF和MCP-1，并与其他免疫细胞相互作用
	LSEC	LSEC毛细血管化，获得基底膜，引起LSEC 功能障碍及毛细血管形成	LSEC毛细血管化加重，内皮功能障碍，肝窦内皮及内皮下基底膜脱落，导致肝脏血流动力学异常
肝非细胞成分	ECM	胶原蛋白和纤连蛋白的大量合成，未形成明显的纤维间隔和结节且分布较均匀	Ⅰ型胶原的合成和沉淀显著增加，纤维间隔和结节形成，肝脏结构紊乱，ECM重构过度，异常表达和不均匀分布
	炎性介质	主要为TNF-α、IL-6及IL-1的水平上升，参与炎症的启动与维持，主要表现为促进炎症反应	除TNF-α、IL-6及IL-1的水平上升外，氧化应激产物如ROS也增加，导致铁死亡损伤肝细胞，同时对肝脏结构和功能的影响更为显著，表现为促进纤维化
	生长因子和趋化因子	主要为TGF-β1、PDGF和VEGF表达水平的升高，参与炎症反应，发挥作用的趋化因子主要是MCP-1	其他生长因子如CTGF开始发挥作用，中晚期阶段还表达SDF-1等趋化因子，促进纤维母细胞和免疫细胞的进一步迁移与浸润
注：MCP-1，单核细胞趋化蛋白-1；ROS，活性氧；TGF-β1，转化生长因子β1；VEGF，血管内皮生长因子；CTGF，结缔组织生长因子；SDF-1，基质细胞衍生因子-1。

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