Yueyue Huang: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Fen Wang: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Hao Li: Department of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
ShunYao Xu: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Wenwei Xu: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
XiaoJun Pan: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Yufeng Hu: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Lingjie Mao: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Songzan Qian: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Jingye Pan: Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China. wmupanjingye@126.com. ORCID
sepsis is a life-threatening condition caused by the dysregulated host immune response to infection characterized by excessive secretion of inflammatory factors. AZD4547 is a selective inhibitor of fibroblast growth factor receptors that participates in the inflammatory response. The aim of this study was to investigate the Inflammation-targeting effects and related molecular mechanisms of AZD4547 in sepsis using a cecal ligation and puncture model and RAW264.7 macrophages stimulated with lipopolysaccharide. AZD4547 improved the survival of CLPmice and exhibited a robust protective function against lung damage histologically. Pretreatment with AZD4547 significantly alleviated the expression of the pro-inflammatory factors IL-1β, IL-6, TNF-α, MMP9, and CXCL10 both in vivo and in vitro. In addition, AZD4547 suppressed the proliferative activity of macrophages in lung tissue and RAW264.7 macrophages. In addition, the LPS-induced phosphorylation of key proteins of NF-κB/MAPK/STAT3 pathways in RAW264.7 macrophages, such as p65, IκB-α, Erk1/2, JNK, and STAT3 proteins, could be inhibited by AZD4547 pretreatment. In conclusion, AZD4547 exerts a protective effect against excessive inflammatory damage in septicmice and may have the potential for use as an effective drug for the management of sepsis.
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Grants
81671968/National Natural Science Foundation of China
Critical Care Medicine, Y2015/Medical Innovation Discipline of Zhejiang Province
