新生儿坏死性小肠结肠炎中细胞死亡机制的研究进展

Research Progress on the Mechanism of Cell Death in Neonatal Necrotizing Enterocolitis

关键词:  坏死性小肠结肠炎  程序性坏死  细胞焦亡  铁死亡  细胞广泛凋亡

Key words:  necrotizing enterocolitis  necroptosis  pyroptosis  ferroptosis  PANoptosis

摘要:

坏死性小肠结肠炎(Necrotizing Enterocolitis，NEC)是由多因素作用导致的肠道急性炎症性疾病，是早产儿主要的死亡原因之一。以往的研究认为，细胞凋亡是NEC中肠上皮细胞最主要的死亡形式。但近年来的研究发现，程序性坏死(Necroptosis)、细胞焦亡(Pyroptosis)及铁死亡(Ferroptosis)等非凋亡形式的程序性细胞死亡(Programmed Cell Death，PCD)也可能参与到NEC的发病机制中，不同形式的细胞死亡的信号调节通路不同，可能会相互影响或存在共同的调节机制如细胞广泛凋亡小体(PANoptosome)等。本文综述了非凋亡形式的不同类型程序性细胞死亡方式及其信号调节通路，以及其在NEC中的作用机制，并提出NEC诊断生物标志物或防治的新靶点，以期为临床NEC的预防和管理提供思路。

Abstract:

Necrotizing Enterocolitis (NEC) is an acute inflammatory disease of the intestine caused by multiple factors,and is one of the main causes of death in premature infants.Previous studies have suggested that apoptosis is the most important form of death in NEC midgut epithelial cells.However,recent studies have found that non-apoptotic Programmed Cell Death (PCD) such as necroptosis,pyroptosis and ferroptosis may also be involved in the pathogenesis of NEC.Different forms of cell death have different signal regulation pathways,which may affect each other or have common regulatory mechanisms such as PANoptosome.This article reviews different types of non apoptotic forms of PCD and their signaling regulatory pathways,as well as their mechanisms of action in NEC.It also proposes new diagnostic biomarkers or new targets for prevention and treatment of NEC,in order to provide ideas for the prevention and management of clinical NEC.