Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325000, China.
Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, 325000, China.
Biochem Biophys Res Commun. 2019 Sep 10;517(1):89-95. doi: 10.1016/j.bbrc.2019.07.023. Epub 2019 Jul 11.
Alveolar epithelial type II cells (ATII cells) are the main target cells being damaged and releasing the inflammatory mediators during acute respiratory distress syndrome (ARDS). Extensive apoptosis of epithelial cells leads to the breakdown of the alveolar-epithelial barrier in ARDS. Cyclooxygenase-2 (COX-2) plays an important role in pulmonary inflammatory response. Dexmedetomidine (DEX), a potent selective α2 adrenergic receptor (α2-AR) agonist, presents sedative, anxiolytic, and analgesic effects for anesthetic procedures. DEX has anti-apoptotic and anti-inflammatory properties. Our study demonstrated that DEX exerted anti-apoptotic effect on primary human epithelial cells with the inhibition of caspase activation, which was partly via the α2AR/PI3K/AKT pathway. Moreover, DEX significantly reduced the expression of COX-2 as well as prostaglandinE (PGE) and tumor necrosis factor-α (TNF-α) production induced by lipopolysaccharide (LPS). Our next step is to determine whether DEX can regulate apoptosis in animal models. These results suggest DEX may be a promising therapy for preventing and treating ARDS as well as chronic diseases by directly targeting epithelial cell actions.
肺泡上皮细胞 II 型（ATII 细胞）是急性呼吸窘迫综合征（ARDS）中主要受损并释放炎症介质的靶细胞。上皮细胞的广泛凋亡导致 ARDS 中肺泡上皮屏障的破坏。环氧化酶-2（COX-2）在肺炎症反应中起重要作用。右美托咪定（DEX）是一种强效的选择性α2 肾上腺素能受体（α2-AR）激动剂，具有镇静、抗焦虑和镇痛作用，适用于麻醉程序。DEX 具有抗凋亡和抗炎作用。我们的研究表明，DEX 通过抑制半胱天冬酶的激活对原代人上皮细胞发挥抗凋亡作用，这部分是通过α2AR/PI3K/AKT 途径。此外，DEX 显著降低了脂多糖（LPS）诱导的 COX-2 以及前列腺素 E（PGE）和肿瘤坏死因子-α（TNF-α）的表达。我们的下一步是确定 DEX 是否可以调节动物模型中的细胞凋亡。这些结果表明，DEX 可能通过直接靶向上皮细胞作用成为预防和治疗 ARDS 以及慢性疾病的有希望的治疗方法。
