Keap1-Nrf2-ARE信号通路与系统性硬化症氧化应激的研究进展

Advances in the Keap1-Nrf2-ARE Signaling Pathway and Oxidative Stress in Systemic Sclerosis

系统性硬化症(systemic sclerosis,SSC),也称为硬皮病,是一种病因未明的慢性结缔组织疾病。越来越多的证据表明,氧化应激在系统性硬化症的发生及发展中起关键作用。Keap1-Nrf2-ARE信号通路作为抗氧化反应的主调节通路,其激活可对系统性硬化症病理改变的多个方面产生影响,包括皮肤和内脏器官纤维化、免疫损伤、慢性炎症等。由于Nrf2通路在系统性硬化症中发挥多途径调节作用,发现及研究Nrf2靶向药物已逐渐受到研究者的重视。因此,本文对Keap1-Nrf2-ARE信号通路在系统性硬化症中的作用机制及相关药物的研究进展进行综述,以期指导系统性硬化症的临床治疗。

Systemic sclerosis(SSC),also known as scleroderma,is a chronic connective tissue disease of unknown etiology.There is increasing evidence that oxidative stress plays a key role in the development and progression of systemic sclerosis.Activation of the Keap1-Nrf2-ARE signaling pathway,a master regulatory pathway of the antioxidant response,affects multiple aspects of systemic sclerosis pathology,including skin and visceral organ fibrosis,immune damage,and chronic inflammation.Due to the multiple regulatory effects of the Nrf2 pathway in systemic sclerosis,the discovery and study of Nrf2-targeted drugs has received increasing attention from researchers.Therefore,this article reviews the mechanism of action of Keap1-Nrf2-ARE signaling pathway in systemic sclerosis and the research progress of related drugs,in order to provide guidance for the clinical treatment of systemic sclerosis.