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.

中文翻译：

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褪黑素受体激动剂可通过上调IL-10产生来防止呼吸机引起的急性肺损伤。

背景技术众所周知，高容量或高压力的通气可能损害健康的肺或使受伤的肺恶化。据报道，褪黑素在急性肺损伤的动物模型中有效。褪黑素通过充当直接抗氧化剂并通过褪黑激素受体激活发挥其有益作用。但是，尚不清楚褪黑激素受体激动剂是否对呼吸机诱发的肺损伤（VILI）有保护作用。因此，在这项研究中，我们确定了雷梅替尼（褪黑激素受体激动剂）是否可以减弱VILI，并探讨了可能的保护机制。方法通过高潮气量通气在大鼠模型中诱导VILI。将大鼠随机分为以下几组：对照组，对照组+褪黑激素，对照组+雷米替尼，对照组+鲁z多尔，VILI，VILI +鲁z多尔，VILI +褪黑素，VILI +褪黑素+ Luzindole（褪黑激素受体拮抗剂），VILI +雷美替尼和VILI +雷美替尼+鲁辛多（每组n = 6）。还研究了白介素10（IL-10）在褪黑素或-子介导的针对VILI的保护中的作用。结果Ramelteon治疗显着降低了肺水肿，血清丙二醛水平，支气管肺泡灌洗液（BALF）中的炎性细胞因子浓度，NF-κB活化，iNOS水平和肺组织凋亡。另外，雷米替尼治疗显着增加了肺组织中热休克蛋白70的表达和BALF中IL-10的水平。拉米替丁的保护作用通过施用鲁辛多或抗IL-10抗体而减轻。结论我们的结果表明褪黑激素受体激动剂对VILI具有保护作用，