急性胰腺炎以铁死亡、焦亡、坏死性凋亡为靶点的治疗研究进展  

Therapeutic research progress of targeting ferroptosis,pyroptosis and necroptosis for acute pancreatitis

作　　者：郑华群 姚广涛 ZHENG Huaqun;YAO Guangtao(Shanghai Innovation Center of TCM Health Service,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;不详)

机构地区：[1]上海中医药大学上海中医健康服务协同创新中心,上海201203 [2]上海中医药大学药物安全评价研究中心,上海201203

出　　处：《山东医药》2025年第4期150-154,共5页Shandong Medical Journal

基　　金：上海市科委生物医药科技支撑专项(22S21901300)。

摘　　要：急性胰腺炎(AP)是由胰酶异常激活导致的胰腺组织自身消化疾病,主要症状为突然发作的持续性上腹部疼痛,可能伴随恶心、呕吐、腹胀、发热等症状,重症患者可能出现低血压或休克,且会合并多脏器功能障碍。AP病理机制不够明确,同时缺乏针对性的靶向治疗,因此导致AP的高发病率和病死率。近年来,铁死亡、焦亡和坏死性凋亡等新型细胞程序性死亡机制的深入研究为解析AP发病机制提供了新视角,并推动了靶向治疗的研发。铁死亡是一种铁依赖的脂质过氧化驱动的细胞死亡形式,其核心机制涉及GPX4活性抑制、活性氧积累及含多不饱和脂肪酸链的磷脂的氧化。在AP中,铁死亡通过促进胰腺腺泡细胞膜损伤和炎症反应加剧病情,靶向铁死亡通路可能成为AP治疗的潜在策略。焦亡是由消皮素D介导的炎性细胞死亡,依赖于NLRP3炎症小体激活。尽管焦亡抑制在AP中显示出保护作用,但其与其他死亡通路的交互机制仍需进一步探索。坏死性凋亡由RIPK1/RIPK3/MLKL通路驱动,其激活导致细胞膜破裂及DAMPs释放,加剧AP的炎症级联反应。坏死性凋亡对AP的进展是促进还是抑制尚不明确,靶向调控坏死性凋亡对AP的防治有着积极意义,需进一步明确坏死性凋亡在AP中的时空特异性作用,以优化靶向治疗策略。Acute pancreatitis(AP)is a disease of self-digestion of pancreatic tissue caused by abnormal activation of pancreatic enzymes.The main symptoms are sudden onset of persistent upper abdominal pain,which may be accompanied by symptoms such as nausea,vomiting,abdominal distension,and fever.In severe patients,hypotension or shock may oc-cur,and multiple organ dysfunction may be combined.The pathological mechanism of AP is not clear enough,and at the same time,there is a lack of targeted therapy,which leads to the high mortality and morbidity of AP.In recent years,in-depth research on new cell programmed death mechanisms such as ferroptosis,pyroptosis and necroptosis has provided a new perspective for analyzing the pathogenesis of AP and has promoted the research and development of targeted therapy.Ferroptosis is a form of iron-dependent lipid peroxidation-driven cell death.Its core mechanism involves the inhibition of GPX4 activity,the accumulation of reactive oxygen species,and the oxidation of phospholipids containing polyunsaturated fatty acid chains.In AP,ferroptosis exacerbates the condition by promoting pancreatic acinar cell membrane damage and inflammatory response.Targeting the ferroptosis pathway may become a potential strategy for AP treatment.Pyroptosis is an inflammatory cell death mediated by gasdermin D and depends on the activation of NLRP3 inflammasome.Although py-roptosis inhibition shows a protective effect in AP,the interaction mechanism between it and other death pathways still needs to be further explored.Necroptosis is driven by the RIPK1/RIPK3/MLKL pathway.Its activation leads to cell mem-brane rupture and the release of DAMPs,exacerbating the inflammatory cascade reaction in AP.It is not clear whether necroptosis promotes or inhibits the progression of AP.Targeted regulation of necroptosis has positive significance for the prevention and treatment of AP.It is necessary to further clarify the spatiotemporal specific role of necroptosis in AP in or-der to optimize targeted treatment strategies.

关 键 词：急性胰腺炎 细胞程序性死亡 铁死亡 焦亡 坏死性凋亡 

分 类 号：R576[医药卫生—消化系统]