Isoflurane, an anesthetic, can aggravate the progression of Alzheimer’s disease (AD). Long non-coding RNA β-secretase 1 (BACE1)-antisense transcript (BACE1-AS) and miR-214-3p are related to AD progression. Nevertheless, it is unclear whether BACE1-AS is involved in the development of isoflurane-mediated AD via miR-214-3p. Amyloid beta peptide (Aβ) was employed to construct the AD cell model. The expression of BACE1-AS and miR-214-3p in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aβ and isoflurane was assessed through quantitative reverse transcription polymerase chain reaction (qRT-PCR). The proliferation and apoptosis of Aβ-treated SK-N-SH and SK-N-AS cells were determined via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) or flow cytometry assays, respectively. Protein levels of B cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), CyclinD1, microtubule-associated protein A1/1B-light chain3 (LC3 I/LC3 II), p62 and Beclin1 were detected via western blot analysis. The relationship between BACE1-AS and miR-214-3p was verified by dual-luciferase reporter assay. We found that BACE1-AS was upregulated and miR-214-3p was downregulated in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aβ and isoflurane. Both BACE1-AS depletion and miR-214-3p augmentation restored the suppression of proliferation and the facilitation of apoptosis and autophagy of Aβ-treated SK-N-SH and SK-N-AS cells induced by isoflurane. Importantly, BACE1-AS acted as a sponge for miR-214-3p. Additionally, miR-214-3p silencing reversed the influence of BACE1-AS knockdown on isoflurane-mediated proliferation, apoptosis and autophagy in Aβ-induced SK-N-SH and SK-N-AS cells. In conclusion, BACE1-AS aggravated isoflurane-induced neurotoxicity to AD via sponging miR-214-3p.

异氟醚是麻醉剂，可加重阿尔茨海默氏病（AD）的进展。长的非编码RNAβ分泌酶1（BACE1）反义转录物（BACE1-AS）和miR-214-3p与AD进展有关。然而，尚不清楚BACE1-AS是否通过miR-214-3p参与异氟烷介导的AD的发展。使用淀粉样蛋白β肽（Aβ）来构建AD细胞模型。通过定量逆转录聚合酶链反应（qRT-PCR）评估AD患者血浆以及经Aβ和异氟烷处理的SK-N-SH和SK-N-AS细胞血浆中BACE1-AS和miR-214-3p的表达。通过3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2-H-溴化四氮唑测定Aβ处理的SK-N-SH和SK-N-AS细胞的增殖和凋亡（ MTT）或流式细胞仪检测。通过Western blot检测B细胞淋巴瘤2（Bcl-2），Bcl-2相关X（Bax），CyclinD1，微管相关蛋白A1 / 1B-轻链3（LC3 I / LC3 II），p62和Beclin1的蛋白水平印迹分析。BACE1-AS与miR-214-3p之间的关系已通过双荧光素酶报告基因检测法得以证实。我们发现，AD患者以及用Aβ和异氟烷处理的SK-N-SH和SK-N-AS细胞的血浆中BACE1-AS被上调，而miR-214-3p被下调。BACE1-AS耗竭和miR-214-3p增强都恢复了异氟烷诱导的Aβ处理的SK-N-SH和SK-N-AS细胞的增殖抑制和细胞凋亡以及自噬的促进作用。重要的是，BACE1-AS充当了miR-214-3p的海绵。此外，miR-214-3p沉默可逆转BACE1-AS敲低对异氟烷介导的增殖的影响，Aβ诱导的SK-N-SH和SK-N-AS细胞的凋亡和自噬。总之，BACE1-AS通过海绵miR-214-3p加重了异氟烷对AD的神经毒性。