Zhang Qiuyue, Wu Di, Yang Yang, Liu Tingting, Liu Hongyu
Department of Paediatrics, Harbin, China.
Department of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Cell Physiol Biochem. 2017;42(5):1907-1919. doi: 10.1159/000479609. Epub 2017 Aug 3.
BACKGROUND/AIMS: Dexmedetomidine (Dex), a specific agonist of α2-adrenoceptor, has been reported to have extensive pharmacological effects. In this study, we focused on the protective effect of Dex on hyperoxia-induced acute lung injury and further explored its possible molecular mechanisms.
The model of hyperoxia-induced acute lung injury was established by continuous inhalation of oxygen (FiO2= 0.90) for 7 d in neonatal rats in vivo. The in vitro experiments were carried out in LPS/ATP or hyperoxia-treated RAW264.7 cells. ELISA, western blot, TUNEL staining, and immunohistochemistry staining assays were performed and the commercial kits were used to assess the beneficial effect of Dex on hyperoxia-induced acute lung injury.
According to our results, Dex treatment attenuated hyperoxia-induced acute lung injury via decreasing the lung wet/dry(W/D) weight ratio and mitigating pathomorphologic changes. Moreover, the oxidative stress injury, inflammatory reaction, and apoptosis in lung epithelial cells were inhibited by Dex treatment. In addition, the activation of NLRP3 inflammasome was restrained by Dex both in lung tissue in vivo and RAW264.7 cells in vitro.
These data provide evidence that Dex may ameliorate hyperoxia-induced acute lung injury, which suggests a potential clinical application of Dex in long-term supplemental oxygen therapy.
背景/目的：右美托咪定（Dex）是一种α2肾上腺素能受体特异性激动剂，据报道具有广泛的药理作用。在本研究中，我们重点关注Dex对高氧诱导的急性肺损伤的保护作用，并进一步探讨其可能的分子机制。
通过在新生大鼠体内连续吸入氧气（FiO2 = 0.90）7天建立高氧诱导的急性肺损伤模型。体外实验在LPS/ATP或高氧处理的RAW264.7细胞中进行。进行ELISA、蛋白质印迹、TUNEL染色和免疫组织化学染色分析，并使用商业试剂盒评估Dex对高氧诱导的急性肺损伤的有益作用。
根据我们的结果，Dex治疗通过降低肺湿/干（W/D）重量比和减轻病理形态学变化减轻了高氧诱导的急性肺损伤。此外，Dex治疗抑制了肺上皮细胞中的氧化应激损伤、炎症反应和细胞凋亡。此外，Dex在体内肺组织和体外RAW264.7细胞中均抑制了NLRP3炎性小体的激活。
这些数据提供了证据表明Dex可能改善高氧诱导的急性肺损伤，这表明Dex在长期补充氧疗中具有潜在的临床应用价值。
