山东医药2025，Vol.65Issue(4)：150-154,5.DOI:10.3969/j.issn.1002-266X.2025.04.031
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
摘要
Abstract
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Key words
acute pancreatitis/programmed cell death/ferroptosis/pyroptosis/necroptosis分类
临床医学引用本文复制引用
郑华群,姚广涛..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[J].山东医药,2025,65(4):150-154,5.基金项目
上海市科委生物医药科技支撑专项(22S21901300). （22S21901300）
