Department of Clinical Pharmacy, Dalian Central Hospital, Dalian, China.
Department of Thoracic Surgery, Dalian Central Hospital, Dalian, China.
Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):506-514. doi: 10.1080/21691401.2020.1716780.
Although dexmedetomidine (Dex) has a significant neuroprotective effect in various nerve-damage models, the exact mechanism of which Dex protects cells from oxidative damage is not fully clear. This article recommended the protective effect of Dex on oxidative damage in PC12 cells. The PC12 cells were incubated by hydrogen peroxide (HO) for 24 h and pre-treated by Dex for 30 min. Cell viability, apoptosis, HIF-1α expression and ROS level were detected by CCK-8, apoptosis assay, Western blot and ROS assay, respectively. The miR-199a expression was tested by qRT-PCR. Targeting relationship between miR-199a and HIF-1α was performed by dual luciferase activity assay. The activation of PI3K/AKT/mTOR and Wnt/β-catenin pathways was tested by western blot. Dex attenuated HO-induced oxidative damage, including the decline of cell viability, the raise of apoptosis and the generation of ROS in PC12 cells by down-regulating miR-199a expression. Moreover, Dex up-regulated HIF-1α expression via decreasing miR-199a level in PC12 cells and miR-199a targeted the 3'-UTR of HIF-1α. In addition, Dex activated PI3K/AKT/mTOR and Wnt/β-catenin pathways by declining miR-199a level. This article illustrated the protective effect of Dex on oxidative damage in PC12 cells. Furthermore, Dex prevented PC12 cells from oxidative injury through the regulation of miR-199a/HIF-1α.
虽然右美托咪定（Dex）在各种神经损伤模型中具有显著的神经保护作用，但 Dex 保护细胞免受氧化损伤的确切机制尚不完全清楚。本文推荐 Dex 对 PC12 细胞氧化损伤的保护作用。将 PC12 细胞用过氧化氢（HO）孵育 24 小时，并用 Dex 预处理 30 分钟。通过 CCK-8、凋亡测定、Western blot 和 ROS 测定分别检测细胞活力、凋亡、HIF-1α 表达和 ROS 水平。通过 qRT-PCR 检测 miR-199a 的表达。通过双荧光素酶活性测定检测 miR-199a 与 HIF-1α 之间的靶向关系。通过 Western blot 检测 PI3K/AKT/mTOR 和 Wnt/β-catenin 通路的激活。Dex 通过下调 miR-199a 表达减轻了 HO 诱导的 PC12 细胞氧化损伤，包括细胞活力下降、凋亡增加和 ROS 生成增加。此外，Dex 通过降低 PC12 细胞中 miR-199a 水平上调 HIF-1α 表达，miR-199a 靶向 HIF-1α 的 3'-UTR。此外，Dex 通过降低 miR-199a 水平激活了 PI3K/AKT/mTOR 和 Wnt/β-catenin 通路。本文说明了 Dex 对 PC12 细胞氧化损伤的保护作用。此外，Dex 通过调节 miR-199a/HIF-1α 防止 PC12 细胞发生氧化损伤。
