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Remimazolam Alleviates Ventilator-Induced Lung Injury by Activating TSPO to Inhibit Macrophage Pyroptosis.
Zhang, Lei; Zhao, Dong; Lv, Huayan; Jiang, Xiaofeng.
Afiliación
  • Zhang L; Department of Anesthesiology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 321000 Jinhua, Zhejiang, China.
  • Zhao D; Department of Anesthesiology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 321000 Jinhua, Zhejiang, China.
  • Lv H; Department of Anesthesiology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 321000 Jinhua, Zhejiang, China.
  • Jiang X; Department of Anesthesiology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 321000 Jinhua, Zhejiang, China.
Discov Med ; 36(187): 1600-1609, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39190375
ABSTRACT

BACKGROUND:

Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI.

METHODS:

A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation in vitro. VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments.

RESULTS:

Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1ß, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis.

CONCLUSION:

Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesión Pulmonar Inducida por Ventilación Mecánica / Piroptosis / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Discov Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesión Pulmonar Inducida por Ventilación Mecánica / Piroptosis / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Discov Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos