Prolonged ischemia can result in apoptotic death of vascular endothelial cells and lead to ischemic vascular diseases including vascular dementia, arteriosclerosis and brain oedema. Finding protective strategies to prevent this is therefore an urgent mission. Recent studies have shown that dysregulation of microRNAs (miRNAs) can lead to imbalance of Bcl-2 family proteins and mitochondrial dysfunction, leading to further damage of vascular cells under ischemic conditions. However, whether miRNAs can be used as a drug target for treating vascular diseases is not fully understood. In this study, we observed that the natural product 2,4,5-trihydroxybenzaldehyde (TDB) could effectively inhibit vascular cell apoptosis following oxygen-glucose deprivation/reperfusion (OGD/R) by maintaining mitochondrial membrane potential (MMP) and suppressing activation of the mitochondria-dependent caspase-9/3 apoptosis pathway. Furthermore, we identified miR-34a, a crucial negative regulator of Bcl-2, as a target for the protective effect of TDB on vascular cells. TDB-induced suppression of miR-34a resulted in a significant upregulation of Bcl-2 protein, MMP maintenance, and the survival of vascular cells following OGD/R. Our findings suggest that targeting miR-34a with the natural product TDB may provide a novel strategy for the treatment of ischemic vascular injuries, and demonstrate the therapeutic potential in targeting miRNAs using appropriate small molecules.

中文翻译：

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TDB 通过靶向 miR-34a 增加 Bcl-2 表达，保护血管内皮细胞免受氧糖剥夺/再灌注诱导的损伤。


长时间的缺血会导致血管内皮细胞凋亡，导致缺血性血管疾病，包括血管性痴呆、动脉硬化和脑水肿。因此，寻找预防策略来防止这种情况的发生是一项紧迫的任务。最近的研究表明，microRNA（miRNA）的失调会导致Bcl-2家族蛋白的失衡和线粒体功能障碍，从而导致缺血条件下血管细胞的进一步损伤。然而，miRNA是否可以作为治疗血管疾病的药物靶点尚不完全清楚。在这项研究中，我们观察到天然产物2,4,5-三羟基苯甲醛（TDB）可以通过维持线粒体膜电位（MMP）和抑制线粒体膜电位（MMP）的激活，有效抑制氧糖剥夺/再灌注（OGD/R）后血管细胞凋亡。线粒体依赖性 caspase-9/3 凋亡途径。此外，我们确定了 miR-34a（Bcl-2 的重要负调节因子）作为 TDB 对血管细胞保护作用的靶点。 TDB 诱导的 miR-34a 抑制导致 Bcl-2 蛋白显着上调、MMP 维持以及 OGD/R 后血管细胞的存活。我们的研究结果表明，用天然产物 TDB 靶向 miR-34a 可能为治疗缺血性血管损伤提供一种新策略，并证明使用适当的小分子靶向 miRNA 的治疗潜力。