Pirinixic Acid Protects Against Hemorrhagic Shock by Regulating Neutrophil-Associated Key Genes.

Journal: Shock (Augusta, Ga.)
Published Date: Dec 26, 2025

Abstract

BACKGROUND: The uncontrolled inflammatory cascade triggered by hemorrhagic shock (HS) can exacerbate tissue damage and organ dysfunction. Neutrophils, as the most abundant type of leukocytes, are key mediators of the innate immune response in the early stages of injury. There is a lack of suitable treatments targeting neutrophils in HS. METHODS: We used machine learning algorithms to identify neutrophil-associated key genes in patients with HS and assessed the diagnostic efficacy of these genes. Weighted gene co-expression network analysis and consensus clustering analysis were performed based on the key genes to explore their role in HS. Finally, we predicted the binding of key genes to drug candidates using molecular docking and observed the effects of drug candidates and the expression of key genes in animals with HS. RESULTS: We screened for key genes with good diagnostic efficacy (ARG1, F2RL1, MPP1, RHOG, UPP1) that activate JAK-STAT3 signaling and apoptotic signaling, leading to poor prognosis. Pirinixic acid screened by the Comparative Toxicogenomics Database has good affinity with key genes, and it can significantly restore the level of inflammatory factors and coagulation function in HS rats, protect the function of vital organs, and prolong the survival time. It was confirmed that pirinixic acid may improve neutrophil immunity disorders by acting on MPP1, RHOG, and F2RL1, and thus protect against HS. CONCLUSIONS: The protective effect of pirinixic acid against HS-induced immune dysregulation is closely associated with the neutrophil genes MPP1, RHOG, and F2RL1.

Authors

  • Xiaowei Zhou
    The State Key Laboratory of Ultrasound Engineering in Medicine, College of Biomedical Engineering, Chongqing Medical University, People's Republic of China.
  • Liyong Zou
  • Haoyue Deng
    *Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China and.
  • Yu Zhu
    Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610212, Sichuan, China; Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, Jiangsu, China.
  • Jie Zhang
    College of Physical Education and Health, Linyi University, Linyi, Shandong, China.
  • Qinghui Li
    Department of Burns, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
  • Shijie Zhou
    School of Biomedical Engineering, Dalhousie University, Dentistry Building, 5981 University Avenue, PO BOX 15000, Halifax, NS, B3H 4R2, Canada. [email protected].
  • Liangming Liu
    Department of Shock and Transfusion, State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, China. [email protected].
  • Li Wang
    College of Marine Electrical Engineering, Dalian Maritime University, Dalian, China.
  • Tao Li
    Department of Emergency Medicine, Jining No.1 People's Hospital, Jining, China.

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