Abstract:
Purpose: This study aimed to elucidate the potential molecular mechanisms by which GSRd improves cardiac inflammation and immune environment after MI.
Materials and Methods: The potential target genes of GSRd were predicted using the STITCH database. In vivo, MI mice models were established by left anterior descending ligation and were divided into the sham group, MI + Vehicle group, and MI + GSRd group. DMSO, DMSO, and GSRd 50 μL/day were intraperitoneally injected, respectively. After 28 days, echocardiography, Masson staining, immunofluorescence staining, flow cytometry, RT-PCR, and Western blot were performed. Mice peritoneal macrophages were extracted in vitro, and Western blot was performed after GSRd and/or Akt inhibitor MK2206 intervention.
Results: GSRd significantly improved mouse myocardial function, attenuated cardiac fibrosis, and inhibited inflammation and apoptosis in myocardial tissues after myocardial infarction. Meanwhile, GSRd increased non-classical Ly6C^low Mos/Mps while reduced of classical Ly6C^high Mos/Mps at the same time in myocardial tissues. In addition, GSRd significantly reversed the activity of p-Akt and p-mTOR in the heart Mos/Mps after MI. In vitro studies showed that the activity of p-Akt and p-mTOR in peritoneal macrophages were significantly increased in a dose-dependent manner after GSRd treatment. Furthermore, the AKT inhibitor MK2206 was found to block the enhanced activity of p-Akt and p-mTOR induced by GSRd in peritoneal macrophages.
Conclusion: GSRd can enhance the transformation of Ly6C^high Mos/Mps to Ly6C^low Mos/Mps in mice after MI by activating the Akt/mTOR signaling pathway, inhibiting cardiac dysfunction and promoting cardiac repair.

Keywords: myocardial infarction, ginsenoside rd, monocytes/macrophages, Akt/mTOR


中文翻译：

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人参皂甙 Rd 通过调节单核细胞/巨噬细胞亚群转换促进心肌梗死后的心脏修复

摘要：
目的：本研究旨在阐明 GSRd 改善 MI 后心脏炎症和免疫环境的潜在分子机制。
材料与方法：使用 STITCH 数据库预测 GSRd 的潜在靶基因。在体内，通过左前降结扎法建立MI小鼠模型，分为假手术组、MI+Vehicle组和MI+GSRd组。DMSO、DMSO 和 GSRd 50 μL/天分别腹膜内注射。28天后，进行超声心动图、Masson染色、免疫荧光染色、流式细胞术、RT-​​PCR和Western印迹。体外提取小鼠腹腔巨噬细胞，在GSRd和/或Akt抑制剂MK2206干预后进行Western blot。
结果：GSRd显着改善小鼠心肌功能，减轻心肌纤维化，抑制心肌梗死后心肌组织的炎症和凋亡。同时，GSRd在心肌组织中增加了非经典Ly6C^低Mos/Mps，同时降低了经典Ly6C^高Mos/Mps。此外，GSRd 显着逆转 MI 后心脏 Mos/Mps 中 p-Akt 和 p-mTOR 的活性。体外研究表明，经 GSRd 处理后，腹腔巨噬细胞中 p-Akt 和 p-mTOR 的活性以剂量依赖性方式显着增加。此外，发现 AKT 抑制剂 MK2206 可阻断 GSRd 在腹腔巨噬细胞中诱导的 p-Akt 和 p-mTOR 活性增强。
结论：GSRd可通过激活Akt/mTOR信号通路，抑制心功能障碍，促进心脏修复，增强心肌梗死后小鼠Ly6C^高Mos/Mps向Ly6C^{低Mos/Mps的转化。}

关键词：心肌梗死，人参皂苷rd，单核细胞/巨噬细胞，Akt/mTOR