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  • 标题:Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway
  • 本地全文:下载
  • 作者:Shujun Yang ; Yaodong Song ; Qiaofang Wang
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2021
  • 卷号:11
  • DOI:10.1038/s41598-021-91008-6
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of l-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)–signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2–STAT3 signalling.
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