Progressive macrophage dysfunction and apoptosis are some of the major events that occur during atherogenesis. To further investigate the intrinsic association between atherosclerosis (AS) and macrophage apoptosis and autophagy, cholesterol crystals (CHCs) were used to stimulate RAW264.7 macrophages to establish a macrophage model of advanced AS. Cells in the CHC group were treated with salvianolic acid B (Sal B) to evaluate its protective effects and reveal its underlying molecular mechanism. The results demonstrated that treatments with Sal B significantly improved autophagy dysfunction and reduced the apoptotic rate of CHC‑induced macrophages. Furthermore, Sal B significantly attenuated CHC‑induced release of proinflammatory factors (TNF‑α and IL‑6) by macrophages. Treatment of macrophages with a specific inhibitor of autophagy (3‑methyladenine) significantly reversed Sal B‑mediated effects on autophagy, suggesting that Sal B‑induced autophagy may display a protective effect in CHC‑induced macrophages. Furthermore, pretreatment of CHC‑induced macrophages with insulin significantly decreased Sal B‑induced autophagy, indicating that the Akt/mTOR signaling pathway may serve as a critical mediator in regulating Sal B‑mediated cell death. Taken together, the present study demonstrated that Sal B improved autophagic dysfunction and reduced the apoptosis of CHC‑induced macrophages via inhibiting the Akt/mTOR signaling pathway.

中文翻译：

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丹酚酸 B 通过抑制 Akt/mTOR 信号通路改善自噬功能障碍并减少胆固醇晶体诱导的巨噬细胞的凋亡。


进行性巨噬细胞功能障碍和细胞凋亡是动脉粥样硬化形成过程中发生的一些主要事件。为了进一步研究动脉粥样硬化（AS）与巨噬细胞凋亡和自噬之间的内在关联，采用胆固醇晶体（CHC）刺激RAW264.7巨噬细胞，建立晚期AS巨噬细胞模型。 CHC组的细胞用丹酚酸B（Sal B）处理，以评估其保护作用并揭示其潜在的分子机制。结果表明，Sal B 治疗显着改善了自噬功能障碍，并降低了 CHC 诱导的巨噬细胞的凋亡率。此外，Sal B 显着减弱 CHC 诱导的巨噬细胞释放促炎因子（TNF-α 和 IL-6）。用特定的自噬抑制剂（3-甲基腺嘌呤）处理巨噬细胞可显着逆转 Sal B 介导的自噬作用，表明 Sal B 诱导的自噬可能对 CHC 诱导的巨噬细胞表现出保护作用。此外，用胰岛素预处理 CHC 诱导的巨噬细胞显着降低 Sal B 诱导的自噬，表明 Akt/mTOR 信号通路可能作为调节 Sal B 介导的细胞死亡的关键介质。综上所述，本研究表明 Sal B 通过抑制 Akt/mTOR 信号通路改善自噬功能障碍并减少 CHC 诱导的巨噬细胞凋亡。