Department of Anesthesiology, The First Affiliated Hospital of Jiamusi University, No.348, dexiang Street, Xiangyang District, Jiamusi, 154002, Heilongjiang Province, People's Republic of China.
Department of Anesthesiology, Second Department of Jiamusi Central Hospital, Jiamusi, 154002, Heilongjiang Province, People's Republic of China.
Neurotox Res. 2023 Oct;41(5):471-480. doi: 10.1007/s12640-023-00653-4. Epub 2023 Sep 1.
Dexmedetomidine (Dex) is reported to play a neuroprotective role in Alzheimer's disease (AD). However, the specific mechanism remains unclear. Figure out the underlying molecular mechanism of Dex regulating nerve cell apoptosis in the AD model. The AD model in vitro was established after SH-SY5Y cells were treated with Aβ1 - 42 at (10 μM) for 24 h. The interaction among UPF1, lncRNA SNHG14, and HSPB8 was verified by RIP assay. Cell viability, apoptosis, the level of genes, and proteins were detected by CCK-8 assay, flow cytometry, Western blot, and qRT-PCR, respectively. Dex downregulated lncRNA SNHG14 level and inhibited apoptosis of nerve cells. LncRNA SNHG14 overexpression reversed the inhibitory effect of Dex on nerve cell apoptosis in the AD model. LncRNA SNHG14 attenuated HSPB8 mRNA stability by recruiting UPF1. HSPB8 overexpression inhibited apoptosis of nerve cells in the AD model. Moreover, HSPB8 knockdown reversed the inhibitory effect of Dex on nerve cell apoptosis in the AD model. Our study demonstrated that Dex promoted HSPB8 expression via inhibiting the lncRNA SNHG14/UPF1 axis to inhibit nerve cell apoptosis in AD.
右美托咪定（Dex）在阿尔茨海默病（AD）中发挥神经保护作用。然而，具体机制尚不清楚。探讨 Dex 调节 AD 模型中神经细胞凋亡的潜在分子机制。用 Aβ1-42（10 μM）处理 SH-SY5Y 细胞 24 h 后，建立体外 AD 模型。通过 RIP 测定验证 UPF1、lncRNA SNHG14 和 HSPB8 之间的相互作用。通过 CCK-8 测定、流式细胞术、Western blot 和 qRT-PCR 分别检测细胞活力、凋亡、基因和蛋白水平。Dex 下调 lncRNA SNHG14 水平并抑制神经细胞凋亡。lncRNA SNHG14 过表达逆转了 Dex 对 AD 模型中神经细胞凋亡的抑制作用。lncRNA SNHG14 通过募集 UPF1 减弱 HSPB8 mRNA 的稳定性。HSPB8 过表达抑制 AD 模型中神经细胞的凋亡。此外，HSPB8 敲低逆转了 Dex 对 AD 模型中神经细胞凋亡的抑制作用。本研究表明，Dex 通过抑制 lncRNA SNHG14/UPF1 轴促进 HSPB8 表达，从而抑制 AD 中的神经细胞凋亡。
