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  3. Atorvastatin combined with imipenem alleviates lung injury in sepsis by inhibiting neutrophil extracellular trap formation via the ERK/NOX2 signaling pathway

Atorvastatin combined with imipenem alleviates lung injury in sepsis by inhibiting neutrophil extracellular trap formation via the ERK/NOX2 signaling pathway

  • Free Radic Biol Med. 2024 May 3:220:179-191. doi: 10.1016/j.freeradbiomed.2024.05.006.
Yue Zhang 1,  Di Wu 2,  Qishun Sun 3,  Zhen Luo 4,  Yuhao Zhang 5,  Bowei Wang 6,  Wenting Chen 7
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou, Guangdong, 510515, China. Electronic address: Zhangyuee012@163.com.
  • 2 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou, Guangdong, 510515, China. Electronic address: wu_d99@163.com.
  • 3 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou, Guangdong, 510515, China. Electronic address: sunqishun12345@126.com.
  • 4 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou, Guangdong, 510515, China. Electronic address: 1759412783@qq.com.
  • 5 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou, Guangdong, 510515, China. Electronic address: 2235599171@qq.com.
  • 6 Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: 81297810@qq.com.
  • 7 Department of Anesthesiology, Nanfang Hospital, Southern Medical University, The Key Laboratory of Precision Anesthesia & Perioperative Organ Protection, Guangzhou, Guangdong, 510515, China. Electronic address: chenwenting326@126.com.
PMID: 38704053 DOI: 10.1016/j.freeradbiomed.2024.05.006
Abstract

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic Microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and Other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.

Keywords

Atorvastatin; ERK; Imipenem; Lung injury; NOX2; Neutrophil extracellular trap; Sepsis.

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