调节性细胞死亡及其靶向治疗在炎症性肠病中的研究进展

Research progress of regulatory cell death and its targeted therapy in inflammatory bowel disease

摘要:

炎症性肠病（IBD）是一组累及胃肠道的慢性非特异性炎症疾病，其发病机制复杂，肠黏膜屏障受损是核心环节，各种病理刺激诱发肠上皮细胞异常死亡，为肠道细菌入侵肠壁并引发炎症反应提供病理基础。近年来，除凋亡、自噬、坏死性凋亡外，焦亡、铁死亡、铜死亡等新型调节性细胞死亡（RCD）均已被证实参与IBD的疾病进展。多种RCD方式可通过调控肠黏膜屏障、免疫反应及肠道微生物等影响IBD的疾病进展，通过靶向RCD治疗有效缓解结肠炎症。该文全面、系统地总结了各种RCD参与IBD的发病机制，旨在全面了解RCD调控IBD的相关机制，并为其临床治疗提供新的靶点和思路。

Abstract:

Inflammatory bowel disease (IBD) comprises a group of chronic non-specific inflammatory conditions affecting the gastrointestinal tract. The pathogenesis of IBD is complex, with damage to the intestinal mucosal barrier being a central component. Various pathological stimuli trigger abnormal cell death in intestinal epithelial cells, providing the pathological basis for bacterial invasion of the intestinal wall and subsequent inflammatory reactions. In recent years, in addition to apoptosis, autophagy, and necroptosis, various novel forms of regulated cell death (RCD), such as pyroptosis, ferroptosis, and copper-dependent cell death, have been implicated in the progression of IBD. Multiple forms of RCD can modulate the intestinal mucosal barrier, immune responses, and gut microbiota, impacting the progression of IBD. Targeting RCD for therapy effectively alleviates colonic inflammation. This paper comprehensively and systematically summarizes the mechanisms by which various forms of RCD contribute to the pathogenesis of IBD, aiming to provide a comprehensive understanding of the regulatory mechanisms of RCD in IBD and offer new targets and strategies for clinical treatment.