活性氧/活性氮与NF-κB信号通路级联交互在肝纤维化中的作用

闵远骞; 李姗; 刘湘花; 杨艺; 李宁宁; 禄保平

doi:10.3969/j.issn.1001-5256.2023.06.031

活性氧/活性氮与NF-κB信号通路级联交互在肝纤维化中的作用

DOI: 10.3969/j.issn.1001-5256.2023.06.031

闵远骞^1a,
李姗^1b,
刘湘花^1c,
杨艺^1b,
李宁宁²,
禄保平^1d, , ,

1a.
河南中医药大学第二临床医学院，郑州 450046
1b.
河南中医药大学医学院，郑州 450046
1c.
河南中医药大学中医药科学院，郑州 450046
1d.
河南中医药大学肝病研究中心，郑州 450046
2.
河南医学高等专科学校，郑州 451191

基金项目:

河南省中医药科学研究专项 (2022ZY1167);

河南省高等学校青年骨干教师培养计划 (2021GGJS084);

河南省高等学校重点科研项目 (21B310003)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：闵远骞负责撰写论文及绘制图片；李姗负责课题设计及修改论文；李宁宁、刘湘花、杨艺负责文献检索及整理；禄保平负责拟定写作思路及最后定稿。

详细信息

通信作者:
禄保平，lbp1921@sohu.com (ORCID: 0000-0002-3707-2185)

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出版历程
- 收稿日期: 2022-10-18
- 录用日期: 2022-11-16
- 出版日期: 2023-06-20

Research advances in the cascade interaction between reactive oxygen species/reactive nitrogen species and the NF-κB signaling pathway in liver fibrosis

Yuanqian MIN^1a,
Shan LI^1b,
Xianghua LIU^1c,
Yi YANG^1b,
Ningning LI²,
Baoping LU^{1d
, ,
,}

1a.
The Second Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, China
1b.
School of Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China
1c.
Academy of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China
1d.
Institute of Hepatology, Henan University of Chinese Medicine, Zhengzhou 450046, China
2.
Henan Medical College, Zhengzhou 451191, China

Research funding:

The Special Research Project of Traditional Chinese Medicine in Henan Province (2022ZY1167);

The Training Program for Young Scholars in Universities of Henan Province (2021GGJS084);

The Important Scientific Research Project of Universities in Henan Province (21B310003)

More Information

Corresponding author: LU Baoping, lbp1921@sohu.com (ORCID: 0000-0002-3707-2185)

摘要

摘要: 肝纤维化是慢性肝损伤后组织修复过程中的代偿反应，也是诸多慢性肝病发展必经的病理过程。在病理状态下，肝脏氧化系统与抗氧化系统失衡，造成活性氧/活性氮产生过多或清除不足，诱导肝细胞损伤，扩大炎症反应，促进肝纤维化的发生发展。NF-κB作为炎症反应和氧化应激的主调控器，在肝纤维化进程中发挥关键作用。因此，活性氧/活性氮与NF-κB信号通路的级联交互关系对于进一步阐明肝纤维化的发病机制，探索有效的防治策略起到重要的指导作用。本文即对两者之间的交互关系及在肝纤维化进程中的重要作用进行综述和讨论，以期为肝纤维化的靶向治疗提供策略和参考。
- 肝纤维化 /
- 氧化性应激 /
- 活性氧 /
- 活性氮 /
- NF-κB
Abstract: Liver fibrosis is a compensatory response in the process of tissue repair after chronic liver injury, and it is also a necessary pathological process in the progression of a variety of chronic liver diseases. In the pathological state, the imbalance between hepatic oxidative system and antioxidant system can lead to the excessive production or insufficient clearance of reactive oxygen species (ROS)/reactive nitrogen species (RNS), which may induce the injury of hepatocytes, expand inflammatory response, and promote the development and progression of liver fibrosis. As a master regulator of oxidative stress and inflammatory response, NF-κB plays a key role in the process of liver fibrosis. Therefore, the cascade interaction between ROS/RNS and the NF-κB signaling pathway plays a guiding role in further clarifying the pathogenesis of liver fibrosis and exploring effective prevention and treatment strategies. This article reviews and discusses the interaction between ROS/RNS and the NF-κB signaling pathway and its important role in the progression of liver fibrosis, so as to provide strategies and references for targeted therapy for liver fibrosis.
- Liver Fibrosis /
- Oxidative Stress /
- Reactive Oxygen Species /
- Reactive Nitrogen Species /
- NF-kappa B

HTML全文

图 1 ROS/RNS与NF-κB信号通路的级联交互

Figure 1. The cross-link between ROS/RNS and NF-κB signaling pathway

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表 1 肝纤维化时ROS/RNS与NF-κB级联交互作用相关文献回顾

Table 1. Literature review of the cross-link between ROS/RNS and NF-κB signaling pathway in liver fibrosis

实验药品	模型	影响	机制	文献
三七总皂苷	非酒精性脂肪肝大鼠	炎症反应↓；纤维化↓	NO/iNOS↓；NF-κB↓	[31]
山奈素	高脂饮食诱导肥胖小鼠	炎症损伤↓；抗氧化能力↑	TLR4↓；NF-κB↓；IκB↑；MDA↓；GSH/CAT/T-AOC/SOD↑	[32]
知母皂苷	高脂饮食诱导肥胖小鼠	炎症损伤↓；氧化应激↓；抗氧化能力↑	p-NF-κB↓；Nrf2/HO-1↑；MDA↓；T-AOC/GSH-Px↑	[33]
橙皮素	高脂饮食诱导NAFLD大鼠	炎症反应↓；氧化应激↓；纤维化↓	PI3K/AKT-Nrf2↑；ROS↓；NF-κB↓	[34]
脱落酸	TAA诱导肝纤维化小鼠	炎症反应↓；氧化应激↓；纤维化↓	肝细胞凋亡因子(如: caspase-3；Bcl-2)↓；NF-κB↓；MDA↓；SOD/GSH↑	[35]
Maresin-1	二乙基亚硝胺诱导肝纤维化大鼠	炎症反应↓；氧化应激↓；抗氧化能力↑	NF-κB↓; Nrf2↑; ROS↓; TGF-β↓	[36]
黄芩苷	TAA诱导肝硬化大鼠	炎症反应↓；氧化应激↓；纤维化↓	NF-κB/IL-6↓; NF-κB/NLRP3炎症小体↓；IL-1↓；NOX4/iNOS↓	[37]
白花丹素(PL)	CCl₄诱导肝纤维化大鼠	氧化应激↓；纤维化↓	NOX4↓；ROS↓；NF-κB↓；α-SMA↓；collagen Ⅲ↓	[38]
甲氧基丁香酚	人和鼠HSC(试管内)(ⅰ) CCl₄诱导肝纤维化小鼠(ⅱ)	炎症损伤↓；纤维化↓	PPAR-γ↑；ROS/RNS↓；NF-κB；纤维化基因mRNA↓；HSC活化↓	[39]
缺乏无活性菱形蛋白2 (iRhom2)敲除	敲除iRhom2的L02细胞(ⅰ)“酒精-吡唑-玉米油”混合物灌胃诱导酒精性肝纤维化小鼠(ⅱ)	炎症反应↓；氧化应激↓；纤维化↓	炎症细胞因子(如: IL-1β、TNF-α)；TACE/NF-κB↓；MDA↓；OH^-/SOD/GSH/T-AOC正常	[40]
Shorthairpin RNA	HBV感染诱导肝纤维化小鼠	炎症反应↓；氧化应激↓；纤维化↓	PPAR-γ↑；ROS/RNS↓；NF-κB↓；TGF-β↓；PRDX1↓；GSTP1↑；α-SMA↓；HSC活化↓	[41]
4-羟基-2(3H)- 苯并噁唑酮(HBOA)	CCl₄诱导肝纤维化大鼠	炎症反应↓；氧化应激↓；纤维化↓	TGF-β1\smad2/3\smad4\α-SMA↓；smad7↑；NF-κB↓；HSC活化↓；MDA↓；ROS↓；GSH/GSH-Px/SOD↑	[42]
注：T-AOC，总抗氧化能力；GSH-Px，谷胱甘肽过氧化物酶；PPAR-γ，过氧化物酶体增殖物激活受体γ；TACE，肿瘤坏死因子-α转换酶；PRDX1，过氧化还原酶1重组蛋白；GSTP1，谷胱甘肽S转移酶P1。↓，下降/抑制；↑，上升/激活。

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