Department of Cardiology, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, China.
Department of Anesthesiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China.
Ann Clin Lab Sci. 2024 Jan;54(1):35-46.
Acute myocardial infarction (AMI) poses a serious burden on public health. Shenmai Injection (SMI) has been reported to have a cardioprotective effect and is used clinically attributed to its targeting of ferroptosis. This study aims to explore the underlying mechanisms of SMI in treating AMI through the application of network pharmacology analysis.
This study utilized network pharmacology to identify the bioactive ingredients and potential targets of SMI in treating AMI. A rat model of AMI was created by ligating the coronary arteries of rats, and a cell model was established by subjecting H9c2 cells to oxygen-glucose deprivation (OGD) to reveal the cardioprotective effects of SMI. Western blotting was employed to measure protein expressions, while hematoxylin-eosin staining was used to observe relevant pathological changes. Enzyme linked immunosorbent assay was conducted to measure the levels of biomarkers associated with cardiac injury and oxidative stress.
A comprehensive analysis revealed a total of 225 putative targets of SMI in the context of AMI which exerted regulatory effects on numerous pathways and targeted multiple biological processes. AKT1 was identified as a core target mediating the effects of SMI on AMI by topological analysis. experiments revealed that SMI attenuated myocardial injury, oxidative stress, and ferroptosis in rats with AMI. Furthermore, SMI was found to enhance the expression levels of p-AKT1 and p-mTOR proteins in the myocardial tissues of rats afflicted with AMI. Similar findings were also observed in H9c2 cells subjected to OGD. Of particular interest, the suppression of OGD-induced iron accumulation, oxidative stress, and ferroptosis-associated proteins by SMI in H9c2 cells was reversed upon inhibition of the AKT1/mTOR pathway via MK2206.
This study revealed that SMI exerts a protective effect against myocardial injury and ferroptosis caused by AMI via the activation of the AKT1/mTOR pathway.
急性心肌梗死（AMI）对公共健康造成严重负担。参麦注射液（SMI）具有心脏保护作用，临床应用归因于其对铁死亡的靶向作用。本研究旨在通过网络药理学分析探讨 SMI 治疗 AMI 的潜在机制。
本研究利用网络药理学方法鉴定 SMI 治疗 AMI 的生物活性成分和潜在靶点。结扎大鼠冠状动脉建立 AMI 大鼠模型，通过氧葡萄糖剥夺（OGD）建立 H9c2 细胞模型，揭示 SMI 的心脏保护作用。采用 Western blot 检测蛋白表达，苏木精-伊红染色观察相关病理变化。酶联免疫吸附法检测与心脏损伤和氧化应激相关的生物标志物水平。
综合分析显示，SMI 治疗 AMI 共有 225 个潜在靶点，这些靶点对多种途径产生调节作用，靶向多个生物学过程。拓扑分析发现 AKT1 是 SMI 对 AMI 作用的核心靶点。实验表明，SMI 减轻 AMI 大鼠心肌损伤、氧化应激和铁死亡。此外，SMI 还可增强 AMI 大鼠心肌组织中 p-AKT1 和 p-mTOR 蛋白的表达水平。在 H9c2 细胞 OGD 模型中也观察到类似结果。有趣的是，通过 MK2206 抑制 AKT1/mTOR 通路，可逆转 SMI 抑制 OGD 诱导的铁积累、氧化应激和铁死亡相关蛋白表达。
本研究表明，SMI 通过激活 AKT1/mTOR 通路，对 AMI 引起的心肌损伤和铁死亡发挥保护作用。
