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Background <p>This study aimed to investigate the effects of the GABA<sub>A</sub> receptor and the potential relationship between GABA/ GABA<sub>A</sub> receptor signalling and aquaporin-1 in acute lung injury (ALI).</p> Methods <p>Fifty-six male Wistar albino rats (220–240&#xa0;g) were divided into seven groups. Two groups received intraperitoneal diazepam at 5 or 10&#xa0;mg/kg. In two other groups, 0.1&#xa0;mg/kg flumazenil was administered five minutes after diazepam. Thirty minutes after the final treatment, all groups except the healthy controls were subjected to an LPS- induced ALI model. Lung tissue were collected 24&#xa0;h after LPS administration and analysed using histopathological, molecular, and biochemical methods.</p> Results <p>In the present study, it was found that aquaporin-1, which plays an important regulatory role in LPS-damaged lung tissue, decreased and the weight of lung tissue increased in wet/dry analysis of a murine model of ALI. The levels of IL-1β, IL-6, and TNF-α were found to be elevated. Additionally, in groups treated with the GABA<sub>A</sub> receptor modulator diazepam, the levels of these inflammatory cytokines were significantly reduced and in parallel a significant increase in aquaporin-1 expression was observed.</p> Conclusion <p>Diazepam, acting as a GABA<sub>A</sub> receptor modulator, may alleviate ALI by reducing inflammation and enhancing aquaporin-1 expression via GABA<sub>A</sub> receptor activation.</p>

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Understanding the relationship between lung GABAA receptors and aquaporin-1: a new therapeutic approach for acute lung injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Hamza Halici,
  • Zeynep Karakoy,
  • Elif Cadirci,
  • Zekai Halici,
  • Bengul Ozdemir,
  • Erdem Toktay

摘要

Background

This study aimed to investigate the effects of the GABAA receptor and the potential relationship between GABA/ GABAA receptor signalling and aquaporin-1 in acute lung injury (ALI).

Methods

Fifty-six male Wistar albino rats (220–240 g) were divided into seven groups. Two groups received intraperitoneal diazepam at 5 or 10 mg/kg. In two other groups, 0.1 mg/kg flumazenil was administered five minutes after diazepam. Thirty minutes after the final treatment, all groups except the healthy controls were subjected to an LPS- induced ALI model. Lung tissue were collected 24 h after LPS administration and analysed using histopathological, molecular, and biochemical methods.

Results

In the present study, it was found that aquaporin-1, which plays an important regulatory role in LPS-damaged lung tissue, decreased and the weight of lung tissue increased in wet/dry analysis of a murine model of ALI. The levels of IL-1β, IL-6, and TNF-α were found to be elevated. Additionally, in groups treated with the GABAA receptor modulator diazepam, the levels of these inflammatory cytokines were significantly reduced and in parallel a significant increase in aquaporin-1 expression was observed.

Conclusion

Diazepam, acting as a GABAA receptor modulator, may alleviate ALI by reducing inflammation and enhancing aquaporin-1 expression via GABAA receptor activation.