Pretreatment with chitosan oligosaccharides attenuate experimental severe acute pancreatitis via inhibiting oxidative stress and modulating intestinal homeostasis

• 作者: Qi-xiang Mei Jun-hui Hu Ze-hua Huang Jun-jie Fan Chun-lan Huang Ying-ying Lu Xing-peng Wang Yue Zeng
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（6）
• 所属期刊栏目: Gastrointestinal Pharmacology
• 页码范围: 942-953
• 页数: 12页
• 语种: 英文

摘要

Severe acute pancreatitis(SAP)is a severe acute abdominal disease.Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis.Chitosan oligosaccharides(COS)possess antioxidant activity that are effective in treating various inflammatory diseases.In this study we explored the potential therapeutic effects of COS on SAP and underlying mechanisms.Mice were treated with COS(200 mg·kg-1·d-1,po)for 4 weeks,then SAP was induced in the mice by intraperitoneal injection of caerulein.We found that COS administration significantly alleviated the severity of SAP:the serum amylase and lipase levels as well as pancreatic myeloperoxidase activity were significantly reduced.COS administration suppressed the production of proinflammatory cytokines(TNF-α,IL-1β,CXCL2 and MCP1)in the pancreas and ileums.Moreover,COS administration decreased pancreatic inflammatory infiltration and oxidative stress in SAP mice,accompanied by activated Nrf2/HO-1 and inhibited TLR4/NF-κB and MAPK pathways.We further demonstrated that COS administration restored SAP-associated ileal damage and barrier dysfunction.In addition,gut microbiome analyses revealed that the beneficial effect of COS administration was associated with its ability to improve the pancreatitis-associated gut microbiota dysbiosis;in particular,probiotics Akkermansia were markedly increased,while pathogenic bacteria Escherichia-Shigella and Enterococcus were almost eliminated.The study demonstrates that COS administration remarkably attenuates SAP by reducing oxidative stress and restoring intestinal homeostasis,suggesting that COS might be a promising prebiotic agent for the treatment of SAP.