CC亚族趋化因子及其受体在慢性肝病中的作用及机制

张子欣; 李晖; 王佳慧; 陶雨静; 曾小晏

doi:10.12449/JCH240528

CC亚族趋化因子及其受体在慢性肝病中的作用及机制

DOI: 10.12449/JCH240528

张子欣^{1, 2},
李晖^1, , ,,
王佳慧²,
陶雨静^{1, 2},
曾小晏^{1, 2}

1.
成都中医药大学附属医院中心实验室，成都 610072
2.
成都中医药大学临床医学院，成都 610072

基金项目:

国家自然科学基金面上项目 (82274323)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：张子欣负责撰写论文；王佳慧，陶雨静，曾小晏参与收集文献，修改论文；李晖负责拟定写作思路，指导文章撰写并最后定稿。

详细信息

通信作者:
李晖， 1400124746@qq.com （ORCID： 0000-0002-5919-1396）

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出版历程
- 收稿日期: 2023-10-19
- 录用日期: 2023-12-12
- 出版日期: 2024-05-25

Role and mechanism of CC chemokines and their receptors in chronic liver diseases

Zixin ZHANG^{1, 2},
Hui LI^{1
, ,
,},
Jiahui WANG²,
Yujing TAO^{1, 2},
Xiaoyan ZENG^{1, 2}

1.
Central Laboratory，The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine，Chengdu 610072，China
2.
School of Clinical Medicine，Chengdu University of Traditional Chinese Medicine，Chengdu 610072，China

Research funding:

General Program of the National Natural Science Foundation of China (82274323)

More Information

Corresponding author: LI Hui， 1400124746@qq.com （ORCID： 0000-0002-5919-1396）

摘要

摘要: 近年来，慢性肝病的发病率持续上升，如慢性乙型肝炎、非酒精性脂肪性肝病、肝纤维化、肝硬化、肝细胞癌等，且发病年龄逐渐呈现低龄化趋势。目前许多CC亚族趋化因子在慢性肝病中的作用得到了证实，本文对近年来影响慢性肝病的CC亚家族趋化因子及其受体的研究进展进行总结，探讨其在慢性肝病中的应用潜力，以期为慢性肝病的防治研究提供新思路。
- 肝疾病 /
- 趋化因子类 /
- 受体，趋化因子
Abstract: In recent years， the incidence rate of chronic liver diseases continues to rise， such as chronic hepatitis B， nonalcoholic fatty liver disease， liver fibrosis， liver cirrhosis， and hepatocellular carcinoma， and the age of onset gradually becomes younger. At present， the role of many CC chemokines in chronic liver diseases has been confirmed. This article summarizes the research advances in CC chemokines and their receptors that affect chronic liver diseases in recent years and explore their potential application in chronic liver diseases， so as to provide new ideas for the prevention and treatment of chronic liver diseases.
- Liver Diseases /
- Chemotactic Factors /
- Receptors， Chemokine

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图 1 CC亚族趋化因子及其受体在慢性肝病中的作用机制

Figure 1. Mechanism of CC subfamily chemokines and receptors in chronic liver disease

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表 1 CC亚族趋化因子及其受体在慢性肝病中的作用

Table 1. Role of CC subfamily chemokines and receptors in chronic liver disease

趋化因子	趋化因子受体	在慢性肝病中的作用
CCL1	CCR8	CCR8促进炎性单核细胞向损伤肝脏的迁移，并使其分化为具有促炎表型的巨噬细胞，发挥促纤维化作用
CCL2	CCR2	CCL2与其受体CCR2结合招募单核-巨噬细胞到损伤的肝脏，抑制CCL2的表达，可减少肝纤维化- HCC动物模型中的Ⅰ型胶原、Ⅳ型胶原和病理性血管生成，从而改善肝脏结构紊乱，高浓度CCL2及其受体可对单核/巨噬细胞积聚、炎症过程启动以及纤维蛋白生成产生影响，并促进癌症的发生
CCL3/CCL5	CCR1/CCR5	CCL3表达促进了HSC的增殖和迁移、促进巨噬细胞浸润到肝脏，分化为M1表型，CCL3缺乏可减轻小鼠肝纤维化。CCL3可以向HCC募集白细胞，促进HCC的发生。CCL3是NAFLD进展的致病因素。CCL5可通过ROS的产生、Akt/ERK的信号传导，诱导HSC迁移；并在纤维化和伤口愈合过程中，招募CCR5阳性的肝祖细胞。CCR5和CCR1在慢性肝损伤的情况下可以促进肝纤维化。CVC是CCR2/CCR5双重拮抗剂，通过抑制炎症性FSCN1⁺巨噬细胞和HERC6⁺中性粒细胞的肝脏积聚来改善细胞外基质沉积和肝纤维化。CCL5为HCC诊断的潜在生物标志物，CCL5的灵敏度和特异度较CCL4更高
CCL4		CCL4为HCC诊断的潜在生物标志物
CCL11		CCL11通过刺激Jagged 1的转录以调节HSC的活化，发挥促纤维化的作用
CCL14		CCL14为肿瘤抑制因子，可用于判断HCC患者的预后
CCL15		CCL15的高表达与HCC患者的不良预后相关
CCL16		CCL16通过使HSC失活抑制肝硬化的进展，并可作为肝硬化发生、进展的标志物
CCL17	CCR4	CCL17可募集Th17细胞、细胞毒性T淋巴细胞到慢性乙型肝炎患者的肝组织中，阻断CCR4可重建T淋巴细胞抗病毒的免疫应答，并限制Treg的免疫抑制功能，有望成为慢性乙型肝炎的潜在治疗靶点
CCL19		过表达CCL19，可通过增加肝内CD8⁺T淋巴细胞，快速清除肝内HBV
CCL20	CCR6	CCL20可招募巨噬细胞和HSC，并通过激活HSC，发挥促炎及促肝纤维化的作用
CCL25	CCR9	在NASH小鼠巨噬细胞招募和肝纤维化形成中发挥重要作用。CCR9拮抗剂可阻碍肝纤维化、脂肪性肝炎和HCC进展

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