Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production
Autor: | Geng-Chin Wu, Kun-Lun Huang, Shi-Jye Chu, Wen-I Liao, Chung-Kan Peng, Hsin-Ping Pao |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Ramelteon Receptors Melatonin Lung injury Pharmacology Melatonin receptor Melatonin Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine medicine Animals Melatonin receptor agonist lcsh:RC705-779 Ventilator-induced lung injury medicine.diagnostic_test business.industry Research lcsh:Diseases of the respiratory system respiratory system respiratory tract diseases Interleukin-10 Rats Up-Regulation Interleukin 10 030104 developmental biology Bronchoalveolar lavage Indenes Luzindole business 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists medicine.drug |
Zdroj: | Respiratory Research Respiratory Research, Vol 21, Iss 1, Pp 1-17 (2020) |
ISSN: | 1465-993X 1465-9921 |
Popis: | Background It is well known that ventilation with high volume or pressure may damage healthy lungs or worsen injured lungs. Melatonin has been reported to be effective in animal models of acute lung injury. Melatonin exerts its beneficial effects by acting as a direct antioxidant and via melatonin receptor activation. However, it is not clear whether melatonin receptor agonist has a protective effect in ventilator-induced lung injury (VILI). Therefore, in this study, we determined whether ramelteon (a melatonin receptor agonist) can attenuate VILI and explore the possible mechanism for protection. Methods VILI was induced by high tidal volume ventilation in a rat model. The rats were randomly allotted into the following groups: control, control+melatonin, control+ramelteon, control+luzindole, VILI, VILI+luzindole, VILI + melatonin, VILI + melatonin + luzindole (melatonin receptor antagonist), VILI + ramelteon, and VILI + ramelteon + luzindole (n = 6 per group). The role of interleukin-10 (IL-10) in the melatonin- or ramelteon-mediated protection against VILI was also investigated. Results Ramelteon treatment markedly reduced lung edema, serum malondialdehyde levels, the concentration of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), NF-κB activation, iNOS levels, and apoptosis in the lung tissue. Additionally, ramelteon treatment significantly increased heat shock protein 70 expression in the lung tissue and IL-10 levels in BALF. The protective effect of ramelteon was mitigated by the administration of luzindole or an anti-IL-10 antibody. Conclusions Our results suggest that a melatonin receptor agonist has a protective effect against VILI, and its protective mechanism is based on the upregulation of IL-10 production. |
Databáze: | OpenAIRE |
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