Department of Otolaryngology, Head and Neck Surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China.
Department of Otolaryngology, Baoshan Branch, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai 201900, China.
Curr Pharm Des. 2020;26(33):4185-4194. doi: 10.2174/1381612826666200602144405.
The aim of the present study was to investigate the protective effects of Tanshinone IIA (Tan IIA) on hypoxia-induced injury in the medial vestibular nucleus (MVN) cells.
An in vitro hypoxia model was established using MVN cells exposed to hypoxia. The hypoxia-induced cell damage was confirmed by assessing cell viability, apoptosis and expression of apoptosis-associated proteins. Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment, and the genes potentially involved in the response were predicted using multiple GEO datasets.
The results of the present study showed that Tan IIA significantly increased cell viability, decreased cell apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells. In addition, hypoxia treatment increased oxidative stress in MVN cells, and treatment with Tan IIA reduced the oxidative stress. The expression of SPhase Kinase Associated Protein 2 (SKP2) was upregulated in hypoxia treated cells, and Tan IIA treatment reduced the expression of SKP2. Mechanistically, SKP2 interacted with large-conductance Ca2+-activated K+ channels (BKCa), regulating its expression, and BKCa knockdown alleviated the protective effects of Tan IIA on hypoxia induced cell apoptosis.
The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced cell damage through its anti-apoptotic and anti-oxidative activity via an SKP2/BKCa axis. These findings suggest that Tan IIA may be a potential therapeutic for the treatment of hypoxia-induced vertigo.
本研究旨在探讨丹参酮 IIA（Tan IIA）对内侧前庭核（MVN）细胞缺氧损伤的保护作用。
采用 MVN 细胞缺氧模型，观察缺氧对细胞活力、凋亡及凋亡相关蛋白表达的影响。通过检测氧化应激及相关指标，预测 Tan IIA 作用的潜在相关基因。
研究结果表明，Tan IIA 可显著提高缺氧处理细胞的活力，降低细胞凋亡率和 Bax/Bcl-2 比值。此外，缺氧处理可增加 MVN 细胞的氧化应激，而 Tan IIA 处理可降低氧化应激。缺氧处理可上调细胞中 S 期激酶相关蛋白 2（SKP2）的表达，而 Tan IIA 处理可降低 SKP2 的表达。机制上，SKP2 与大电导钙激活钾通道（BKCa）相互作用，调节其表达，BKCa 敲低可减轻 Tan IIA 对缺氧诱导的细胞凋亡的保护作用。
本研究结果表明，Tan IIA 通过其抗凋亡和抗氧化活性，通过 SKP2/BKCa 轴对缺氧诱导的细胞损伤具有保护作用。这些发现提示 Tan IIA 可能是治疗缺氧性眩晕的潜在治疗药物。
