1st Medical Center of Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China.
Air Force Medical Center, PLA, 30th Fucheng Road, Haidian District, Beijing, 100142, China.
Mol Neurobiol. 2022 Jun;59(6):3504-3511. doi: 10.1007/s12035-022-02757-y. Epub 2022 Mar 26.
Propofol is widely used as an intravenous anesthetic in clinical practice. Previous studies have indicated that propofol induces apoptosis in neurons. Brain-derived neurotrophic factor (BDNF), a neurotrophic factor, is associated with neuronal apoptosis. BDNF-AS, a relatively conserved long non-coding RNA, can reverse the transcription of BDNF. This study aimed to investigate the involvement of BDNF-AS in propofol-induced apoptosis in HT22 cells. HT22 cells were treated with various concentrations of propofol at different time points. BDNF-AS was silenced using BDNF-AS-targeting siRNA. TrkB was antagonized by the TrkB inhibitor, ANA-12. Flow cytometry, quantitative reverse-transcription PCR, and western blotting were performed to analyze apoptosis and the expression of genes and proteins, respectively. In propofol-treated HT22 cells, BDNF-AS was upregulated, and BDNF was downregulated in a time- and dose-dependent manner. BDNF-AS downregulation mediated by siRNA mitigated apoptosis, upregulated the expression of Bcl-2, and downregulated the expression of Bax and caspase-3, 7, and 9. ANA-12 downregulated the expression of Bcl-2, upregulated the expression of Bax and caspase-3, 7, and 9, and increased apoptosis. Our study implied that inhibition of BDNF-AS can decrease propofol-induced apoptosis by activating the BDNF/TrkB pathway. Thus, the BDNF-AS-BDNF/TrkB signaling pathway may be a valuable target for treating propofol-induced neurotoxicity.
异丙酚在临床实践中被广泛用作静脉麻醉剂。先前的研究表明，异丙酚诱导神经元凋亡。脑源性神经营养因子（BDNF）是一种神经营养因子，与神经元凋亡有关。BDNF-AS 是一种相对保守的长链非编码 RNA，可以逆转 BDNF 的转录。本研究旨在探讨 BDNF-AS 在异丙酚诱导的 HT22 细胞凋亡中的作用。用不同浓度的异丙酚处理 HT22 细胞不同时间点。用 BDNF-AS 靶向 siRNA 沉默 BDNF-AS。用 TrkB 抑制剂 ANA-12 拮抗 TrkB。流式细胞术、定量逆转录 PCR 和 Western blot 分别用于分析细胞凋亡以及基因和蛋白的表达。在异丙酚处理的 HT22 细胞中，BDNF-AS 呈时间和剂量依赖性上调，BDNF 呈下调。siRNA 介导的 BDNF-AS 下调减轻了细胞凋亡，上调了 Bcl-2 的表达，下调了 Bax 和 caspase-3、7、9 的表达。ANA-12 下调了 Bcl-2 的表达，上调了 Bax 和 caspase-3、7、9 的表达，增加了细胞凋亡。我们的研究表明，抑制 BDNF-AS 可以通过激活 BDNF/TrkB 通路减少异丙酚诱导的细胞凋亡。因此，BDNF-AS-BDNF/TrkB 信号通路可能是治疗异丙酚诱导的神经毒性的一个有价值的靶点。
