Abstract：
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.
摘要：
据报道,右美托咪定(Dex)在阿尔茨海默病(AD)中起神经保护作用。然而,具体机制尚不清楚.在AD模型中阐明Dex调控神经细胞凋亡的分子机制。将SH-SY5Y细胞用Aβ1-42（10μM）处理24h后，建立了体外AD模型。通过RIP分析验证了UPF1，lncRNASNHG14和HSPB8之间的相互作用。细胞活力，凋亡，基因的水平，并通过CCK-8测定法检测蛋白质，流式细胞术,蛋白质印迹,和qRT-PCR，分别。Dex下调lncRNASNHG14水平并抑制神经细胞凋亡。LncRNASNHG14过表达逆转了Dex对AD模型神经细胞凋亡的抑制作用。LncRNASNHG14通过招募UPF1减弱HSPB8mRNA的稳定性。HSPB8过表达抑制AD模型神经细胞凋亡。此外，HSPB8敲低可逆转Dex对AD模型神经细胞凋亡的抑制作用。我们的研究表明，Dex通过抑制lncRNASNHG14/UPF1轴促进HSPB8的表达，从而抑制AD中神经细胞的凋亡。
