Nrf2信号通路在肝脏缺血再灌注损伤中的保护机制及治疗前景的研究进展

Research progress on the protective mechanisms and therapeutic prospects of the Nrf2 signaling pathway in hepatic ischemia-reperfusion injury

摘要:

肝脏缺血再灌注损伤（HIRI）是肝移植和肝切除术后常见且难以避免的并发症，其发病机制涉及多个病理生理过程，包括氧化应激、无菌性炎症、线粒体功能障碍和细胞凋亡等。核因子红细胞2相关因子2（Nrf2）是细胞抗氧化反应的关键调节因子，其通过激活血红素加氧酶-1、超氧化物歧化酶和谷胱甘肽等抗氧化因子的表达，维持细胞的氧化还原平衡。Nrf2还通过抑制促炎因子的释放及调控炎症信号通路，减轻炎症反应并减少细胞凋亡，从而保护肝脏。该文综述了Nrf2在HIRI中的作用机制，Nrf2激活剂的研究进展及其临床转化前景，并探讨了人工智能、类器官模型等前沿技术在Nrf2研究中的应用价值，旨在为基于Nrf2通路的HIRI防治策略提供理论依据。

Abstract:

Hepatic ischemia-reperfusion injury (HIRI) is a common and unavoidable complication following liver transplantation and hepatectomy. Its pathogenesis involves multiple pathophysiological processes, including oxidative stress, sterile inflammation, mitochondrial dysfunction, and apoptosis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant responses that maintains cellular redox balance by activating the expression of antioxidant factors such as heme oxygenase-1 (HO-1), superoxide dismutase (SOD), and glutathione (GSH). Nrf2 also protects the liver by inhibiting the release of pro-inflammatory factors, regulating inflammatory signaling pathways, reducing inflammatory responses, and decreasing apoptosis. This review summarizes the mechanistic roles of Nrf2 in HIRI, recent advances in Nrf2 activators, and their prospects for clinical translation. Furthermore, it discusses the application potential of cutting-edge technologies such as artificial intelligence and organoid models in Nrf2-related research, aiming to provide a theoretical basis for the prevention and treatment of HIRI through targeting the Nrf2 signaling pathway.