Neutrophils and Neutrophil Extracellular Traps in Hepatic Ischemia–Reperfusion Injury: Molecular Mechanisms and Therapeutic Strategies

Hepatic ischemia-reperfusion injury (HIRI) is an unavoidable clinical challenge in liver transplantation, major hepatectomy and trauma resuscitation, with no approved specific therapeutics to date. As core innate immune effector cells, neutrophils are the central driver of the sterile inflammatory cascade in HIRI. Centered on the Mac-1-Syk core regulatory axis, this review systematically elaborates the neutrophil recruitment cascade and intracellular signaling network in HIRI, focuses on the sequential formation pathways of neutrophil extracellular traps (NETs) and their multi-dimensional injury mechanisms, and dissects the inflammation-thrombosis amplification crosstalk between neutrophils and multiple hepatic non-parenchymal cells. Furthermore, this review clarifies research controversies of core therapeutic targets, analyzes key translational bottlenecks, and proposes a NETs-centered sequential multi-target combination strategy, providing a solid theoretical basis and clear translational direction for the precise targeted therapy of HIRI.