Department of Anesthesiology, Wujin Hospital Affiliated to Jiangsu University (Wujin School of Clinical Medicine, Xuzhou Medical University), Changzhou, Jiangsu, PR China.
Histol Histopathol. 2024 Nov;39(11):1485-1492. doi: 10.14670/HH-18-737. Epub 2024 Mar 25.
Urolithin A (UroA) is well-recognized for its anti-oxidative, anti-inflammatory, and immunomodulatory potentials and has been proven to have neuroprotective effects. Nevertheless, the potential of UroA on bupivacaine (BUP)-induced neurotoxicity has never been reported. Using SH-SY5Y cells to establish a cell model, it was revealed that BUP stimulated cell viability reduction, LDH release increase, and suppression of SIRT1-activated PI3K/AKT signaling in SH-SY5Y cells, whereas UroA treatment caused an effective abrogation of the effects of BUP. Besides, SIRT1 overexpression caused an enhancement in the activity of PI3K/AKT signaling in BUP and UroA co-treated cells, indicating that SIRT1 mediated the activity of PI3K/AKT signaling. Moreover, UroA inhibited BUP-induced apoptosis, oxidative stress, and inflammatory responses in SH-SY5Y cells. However, the effects of UroA on BUP-induced neurotoxicity were all abated by inhibiting SIRT1 or PI3K/AKT signaling through EX527 or LY294002. In conclusion, UroA protected SH-SY5Y cells against BUP-induced injuries through PI3K/AKT signaling in a SIRT1-dependent manner.
尿石素 A（UroA）因其抗氧化、抗炎和免疫调节潜力而广为人知，并已被证明具有神经保护作用。然而，UroA 对布比卡因（BUP）诱导的神经毒性的潜在作用尚未有报道。本研究使用 SH-SY5Y 细胞建立细胞模型，结果表明 BUP 刺激 SH-SY5Y 细胞活力降低、LDH 释放增加和 SIRT1 激活的 PI3K/AKT 信号抑制，而 UroA 处理可有效阻断 BUP 的作用。此外，SIRT1 过表达导致 BUP 和 UroA 共同处理细胞中 PI3K/AKT 信号的活性增强，表明 SIRT1 介导了 PI3K/AKT 信号的活性。此外，UroA 抑制了 BUP 诱导的 SH-SY5Y 细胞凋亡、氧化应激和炎症反应。然而，通过 EX527 或 LY294002 抑制 SIRT1 或 PI3K/AKT 信号，UroA 对 BUP 诱导的神经毒性的作用均被减弱。总之，UroA 通过 SIRT1 依赖性方式保护 SH-SY5Y 细胞免受 BUP 诱导的损伤。
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