炎症性肠病中的坏死性凋亡:一个潜在的治疗靶点

Necroptosis in inflammatory bowel disease:A potential effective target

炎症性肠病(inflammatory bowel diseases,IBD)的发病率近年来呈快速上升趋势,目前尚无有效的方法防止其复发。程序性细胞死亡对维持内环境稳态至关重要。坏死性凋亡作为一种新发现的程序性细胞死亡方式,其在IBD中的作用值得探讨。坏死性凋亡由受体相互作用蛋白激酶1(receptor interacting protein kinase 1,RIPK1)、RIPK3和混合系激酶区域样蛋白(mixed lineage kinase domain-like protein,MLKL)介导,导致细胞肿胀、质膜破裂、细胞内容物流出,继而引起细胞死亡并促进炎症的发生。研究发现IBD患者病变标本的坏死性凋亡水平升高,在IBD动物模型中抑制坏死性凋亡能够减轻炎症程度,表明坏死性凋亡与IBD的发病机制相关。然而,由于细胞坏死性凋亡调控的复杂性及其相关信号分子功能的多样性,其具体机制仍未明确。坏死性凋亡在IBD的发病过程中可能发挥了重要的调控作用,为进一步探究IBD的治疗靶点提供了新的思路和方法。

The morbidity of inflammatory bowel diseases(IBD)is rising rapidly but no curative therapies to prevent its recurrence.Cell death is crucial to maintaining homeostasis.Necroptosis is a newly identified programmed cell death and its roles played in IBD need to be explored.Necroptosis is mediated by receptor interacting protein kinase 1(RIPK1),RIPK3,and mixed lineage kinase domain-like protein(MLKL),which resulted in cell swelling,plasma membrane rupture,intracellular content leaking,and eventually cell death as well as the promotion of inflammation.Studies have found that inhibiting necroptosis alleviated IBD in animal models and IBD patients with an increased level of necroptosis in inflammatory tissues,indicating that necroptosis is related to the pathogenesis of IBD.However,due to the complexity in regulation of necroptosis and the involvement of multiple functions of relevant signaling molecules,the specific mechanism remains elusive.Necroptosis may play a vital regulatory role in the pathogenesis of IBD,which provides a new idea and method for further exploring the therapeutic target of IBD.