Shandong Provincial Medicine and Health Key Laboratory of Clinical Anesthesia, School of Anesthesiology, Weifang Medical University, Weifang, China.
Department of Cardiology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Cardiovasc Transl Res. 2023 Apr;16(2):341-357. doi: 10.1007/s12265-022-10303-3. Epub 2022 Aug 19.
The present study highlights the effects of salvianolic acid B (Sal B) on angiotensin II (Ang II)-activated atrial fibroblasts as well as the associated potential mechanism from the metabonomics perspective. Metabolic profile analysis performed an optimal separation of the Ang II and control group, indicating a recovery impact of Sal B on Ang II-activated fibroblasts (FBs). We found that metabolite levels in the Ang II + Sal B group were reversed to normal. Moreover, 23 significant metabolites were identified. Metabolic network analysis indicated that these metabolites participated in purine metabolism and FoxO signaling pathway. We found that Sal B activated AMP-activated protein kinase (AMPK) phosphorylation, which further promoted FoxO1 activation and increased miR-148a-3p level. We further verified that Sal B modulate the abnormal AMP, phosphocreatine, glutathione (GSH), and reactive oxygen species (ROS) production in Ang II-stimulated FBs. Collectively, Sal B can protect the Ang II-activated FBs from fibrosis and oxidative stress via AMPK/FoxO1/miRNA-148a-3p axis.
本研究从代谢组学角度探讨丹酚酸 B（Sal B）对血管紧张素 II（Ang II）激活的心房成纤维细胞的影响及其相关潜在机制。代谢轮廓分析对 Ang II 组和对照组进行了最佳分离，表明 Sal B 对 Ang II 激活的成纤维细胞（FBs）具有恢复作用。我们发现 Ang II + Sal B 组的代谢物水平恢复正常。此外，鉴定出 23 种有显著差异的代谢物。代谢网络分析表明，这些代谢物参与嘌呤代谢和 FoxO 信号通路。我们发现 Sal B 激活 AMP 激活蛋白激酶（AMPK）磷酸化，进一步促进 FoxO1 激活并增加 miR-148a-3p 水平。我们进一步验证了 Sal B 可以调节 Ang II 刺激的成纤维细胞中异常的 AMP、磷酸肌酸、谷胱甘肽（GSH）和活性氧（ROS）的产生。综上所述，Sal B 可以通过 AMPK/FoxO1/miRNA-148a-3p 轴保护 Ang II 激活的成纤维细胞免受纤维化和氧化应激。
