临床肝胆病杂志2025，Vol.41Issue(4)：722-730,9.DOI:10.12449/JCH250418
咖啡酸在重症急性胰腺炎小鼠模型中的作用及其机制
Role and mechanism of caffeic acid in a mouse model of severe acute pancreatitis
摘要
Abstract
Objective To investigate the effect and potential mechanism of caffeic acid(CA)on severe acute pancreatitis(SAP)induced by caerulein combined with lipopolysaccharide(LPS),and to provide a basis for the research on novel drugs for the treatment of SAP.Methods C57BL/6J mice,aged 6 weeks,were divided into control group,model group,CA group,and octreotide acetate(OA)group,with 6 mice in each group.The mice in the control group were given injection of normal saline,and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP.At 1 hour after the first injection of caerulein,the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours.The general status of the mice was observed after 24 hours of modeling,and serum,pancreas,lung,and colon samples were collected.HE staining was used to observe the histopathological changes of the pancreas and lungs,and the serum levels of α-amylase,lipase,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),alanine aminotransferase,aspartate aminotransferase,and creatinine were measured.RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs;myeloperoxidase(MPO)immunohistochemistry was used to observe the degree of neutrophil infiltration;Western blot was used to measure the activation of nuclear factor-kappa B(NF-κB)and the level of citrullinated histone H3(CitH3),a marker for the formation of neutrophil extracellular traps(NETs),in the pancreas and lungs,as well as the expression level of ZO-1 in colon tissue.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the Dunnett's t-test was used for further comparison between two groups.Results Compared with the control group,the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α-amylase and lipase and the levels of the proinflammatory cytokines IL-6,interleukin-1β(IL-1β),and TNF-α in serum and lung tissue(all P<0.05),as well as significant increases in NF-κB activation,neutrophil infiltration,and the formation of NETs in the pancreas and lungs(all P<0.05).Compared with the model group,the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6,IL-1β,and TNF-α in serum and lung tissue(all P<0.05),as well as significant reductions in NF-κB activation,neutrophil infiltration,and the formation of NETs in the pancreas and lungs(all P<0.05).Conclusion CA can alleviate SAP induced by caerulein combined with LPS in mice,possibly by inhibiting neutrophil recruitment and the formation of NETs.关键词
胰腺炎/小鼠,近交C57BL/咖啡酸/模型,动物Key words
Pancreatitis/Mice,Inbred C57BL/Caffeic Acid/Models,Animal引用本文复制引用
续嗣钰,柳涛,兰路路,薛怡宁,卫威,韩奕,穆素成,宋海燕,杜施霖..咖啡酸在重症急性胰腺炎小鼠模型中的作用及其机制[J].临床肝胆病杂志,2025,41(4):722-730,9.基金项目
上海市卫生健康委卫生行业临床研究专项(202040223) Clinical Research Special Project of Shanghai Municipal Health Commission(202040223) （202040223）
