New research progress of tumor necrosis factor-α signaling pathway regulating alcoholic hepatitis

doi:10.12092/j.issn.1009-2501.2026.07.012

Abstract

Abstract:

Alcoholic hepatitis (AH) is an immunoin flammatory disease of the liver caused by long-term heavy drinking of ethanol and its metabolites. Tumor necrosis factor-α (TNF-α) plays a key regulatory role in the inflammatory response of liver tissue, such as inflammatory cell infiltration, hepatocyte hepatocyte enlargement with steatosis, and fibrous tissue hyperplasia in the confluent area during the process of AH. Therefore, TNF-α regulation of AH-related signaling networks has become a new research hotspot in recent years. This article reviews the mechanism of TNF-α in regulating alcoholic hepatitis from the perspective of signaling networks such as nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, mitogen-activated protein kinase (MAPK) as well as signal transducers and activators of transcription 3 (STAT3), to provide a theoretical basis for the study of the inflammatory response mechanism of AH liver tissue and the development of new drugs.

Key words: alcoholic hepatitis, tumor necrosis factor-α, signaling network, research progress

CLC Number:

R966

Bei TIAN, Mei GUO, Zhiwang WANG, Yue ZHANG, Ping QUAN, Yue ZHAO, Qiwei WANG, Xinyu ZHU, Jing SHAO. New research progress of tumor necrosis factor-α signaling pathway regulating alcoholic hepatitis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(7): 957-964.

Figures/Tables 2

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信号网络	有效组分/ 小分子抑制剂	不同效应及组织病理变化	作用机制	参考文献
NF-κB	PDTC （NF-κB拮抗剂）	缓解氧化应激；降低肝细胞凋亡和肝组织损伤	抑制IκBa磷酸化	[15]
NF-κB	甘蔗糖蜜多酚提取物	阻断炎症级联反应	下调TNF-α、NF-κB的表达	[16]
TLR4	穗花杉双黄酮	减轻肝脏炎症反应	抑制TLR4/NF-κB/TNF-α信号通路	[20]
	TLR4/MD-2抗体	胶原纤维沉积减少；缓解肝纤维化；减少肝细胞凋亡	抑制LPS-TLR4/MD-2-TNF-α信号通路	[21]
	参苓白术散	减少肝细胞脂滴空泡数量；炎性细胞浸润减少	下调TNF-α、TLR4表达	[22]
NLRP3	清肝活血方	降低肝脏脂质累积；减轻炎性细胞浸润	下调TNF-α、NLRP3表达	[26]
NLRP3	黄芪甲苷Ⅳ	减轻肝脏炎症反应	下调TNF-α、NLRP3表达	[27]
MAPK	佛手精油	缓解肝脏组织结构紊乱；抑制炎性细胞浸润	抑制TNF-α、MAPK表达	[30]
MAPK	SB203580 （p38 MAPK抑制剂）	减轻肝脏炎症	下调TNF-α、p38 MAPK表达	[31]
STAT3	AG490 （STAT3抑制剂）	缓解肝脏炎症反应	抑制STAT3磷酸化	[35]
STAT3	Hydroxytyrosol	减轻炎性细胞浸润	抑制STAT3/iNOS/TNF-α信号通路	[36]
mTOR	岩藻多糖	改善肝脏脂质代谢紊乱及肝脏变形	下调TNF-α、p-mTORC1和p-p70S6K表达	[39]
TGF-β1	尖叶假龙胆	降低MDA含量，加速酒精代谢	抑制TNF-α和TGF-β1表达	[42]
IL-6	参麦注射液	改善肝功能；减轻炎症反应	下调TNF-α、IL-6的表达	[43]

信号网络	有效组分/ 小分子抑制剂	不同效应及组织病理变化	作用机制	参考文献
NF-κB	PDTC （NF-κB拮抗剂）	缓解氧化应激；降低肝细胞凋亡和肝组织损伤	抑制IκBa磷酸化	[15]
NF-κB	甘蔗糖蜜多酚提取物	阻断炎症级联反应	下调TNF-α、NF-κB的表达	[16]
TLR4	穗花杉双黄酮	减轻肝脏炎症反应	抑制TLR4/NF-κB/TNF-α信号通路	[20]
	TLR4/MD-2抗体	胶原纤维沉积减少；缓解肝纤维化；减少肝细胞凋亡	抑制LPS-TLR4/MD-2-TNF-α信号通路	[21]
	参苓白术散	减少肝细胞脂滴空泡数量；炎性细胞浸润减少	下调TNF-α、TLR4表达	[22]
NLRP3	清肝活血方	降低肝脏脂质累积；减轻炎性细胞浸润	下调TNF-α、NLRP3表达	[26]
NLRP3	黄芪甲苷Ⅳ	减轻肝脏炎症反应	下调TNF-α、NLRP3表达	[27]
MAPK	佛手精油	缓解肝脏组织结构紊乱；抑制炎性细胞浸润	抑制TNF-α、MAPK表达	[30]
MAPK	SB203580 （p38 MAPK抑制剂）	减轻肝脏炎症	下调TNF-α、p38 MAPK表达	[31]
STAT3	AG490 （STAT3抑制剂）	缓解肝脏炎症反应	抑制STAT3磷酸化	[35]
STAT3	Hydroxytyrosol	减轻炎性细胞浸润	抑制STAT3/iNOS/TNF-α信号通路	[36]
mTOR	岩藻多糖	改善肝脏脂质代谢紊乱及肝脏变形	下调TNF-α、p-mTORC1和p-p70S6K表达	[39]
TGF-β1	尖叶假龙胆	降低MDA含量，加速酒精代谢	抑制TNF-α和TGF-β1表达	[42]
IL-6	参麦注射液	改善肝功能；减轻炎症反应	下调TNF-α、IL-6的表达	[43]

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