Esketamine mitigates mechanical ventilation-induced lung injury in chronic obstructive pulmonary disease rats via inhibition of the MAPK/NF-κB signaling pathway and reduction of oxidative stress.

Autor: Cai SY; Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China; Department of Anesthesiology, Mindong Hospital Affiliated to Fujian Medical University, Fuan 355000, Fujian, China., Liu A; Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China; Department of Anesthesiology, Heze Municipal Hospital, Heze 274000, China., Xie WX; Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China., Zhang XQ; Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China., Su B; Department of Anesthesiology, Heze Municipal Hospital, Heze 274000, China., Mao Y; Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China., Weng DG; Department of Anesthesiology, Mindong Hospital Affiliated to Fujian Medical University, Fuan 355000, Fujian, China. Electronic address: wdgmdyy@163.com., Chen ZY; Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China. Electronic address: chenzy0818@126.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Sep 30; Vol. 139, pp. 112725. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1016/j.intimp.2024.112725
Abstrakt: Purpose: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms.
Methods: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays.
Results: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue.
Conclusion: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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