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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Obstetric and Pediatric Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1621190

Heliox Preconditioning Exerts Pulmonary Protection Efects on Neonatal Acute Respiratory Distress Syndrome by Inhibiting Oxidative Stress and Apoptosis

Provisionally accepted
  • 1Children’s Hospital of Chongqing Medical University, Chongqing, China
  • 2Department of Pediatrics, First Affiliated Hospital of Army Medical University, Chongqing, China

The final, formatted version of the article will be published soon.

Objective: This study aimed to investigate whether heliox preconditioning (HePC) alleviates neonatal acute respiratory distress syndrome (ARDS) by inhibiting oxidative stress and apoptosis, and to explore its potential mechanism.Methods: Blood samples and bronchoalveolar lavage fluid (BALF) were collected from rat pups were randomly divided into control group, sham group, ARDS group, ARDS+CaMKII -group, ARDS+CaMKII + group, and ARDS+HePC group. We also investigated the role of CaMKII by manipulating its expression in vitro. Inflammatory markers, oxidative stress,apoptosis and activation of signaling pathways were assessed using histological staining, ELISA, Western blotting, qRT-PCR , Ca 2+ , immunofluorescence staining, and flow cytometry. Results: In vivo, HePC significantly reduced the expression of CaMKII, inhibited the activation of CaMKII/RyR2, ameliorated the LPS-induced lung histopathological changes in rat pups, reduced lung wet/dry ratios, ROS and MDA levels, and pro-inflammatory cytokine levels, and significantly increased the expression of antioxidant proteins (Nrf2, HO-1 and SOD) and reduced LPS-induced apoptosis. In vitro, overexpression of CaMKII increases oxidative stress and activates RyR2, leading to cytoplasmic Ca 2+ overload and increased apoptosis. HePC can reverse the above reactions by inhibiting the expression of CaMKII. Conclusions: HePC may attenuate oxidative stress through CaMKII and alleviate cytoplasmic Ca 2+ overload by regulating CaMKII/RyR2, which inhibits apoptosis, exerting lung protection against ARDS.

Keywords: heliox preconditioning, neonatal acute respiratory distress syndrome, CaMK-II, anti-oxidative stress, anti-apoptosis

Received: 30 Apr 2025; Accepted: 29 Jul 2025.

Copyright: © 2025 Ma, Shen and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yuan Shi, Children’s Hospital of Chongqing Medical University, Chongqing, China

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