Li Han, Wei Dongsheng, Cao Huimin, Han Yelei, Li Luzhen, Liu Yuting, Qi Jiajie, Wu Xinyue, Zhang Zhe
The First School of Clinical Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People's Republic of China.
Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People's Republic of China.
J Inflamm Res. 2025 Jan 7;18:301-323. doi: 10.2147/JIR.S491535. eCollection 2025.
Myocardial infarction (MI) is a prevalent cardiovascular disorder affecting individuals worldwide. There is a need to identify more effective therapeutic agents to minimize cardiomyocyte damage and enhance cardioprotection. extract is extensively used to treat neurological disorders and peripheral vascular diseases. The aim of this study was to determine the protective effects and mechanisms of ginkgetin on postinfarction cardiomyocytes through bioinformatics and experimental validation.
Bioinformatics analysis was performed to predict the underlying biological mechanisms of ginkgetin in the treatment of MI. Next, we performed further validation through experiments. For in vivo studies, we used coronary ligation to construct an MI rat model. In vitro, oxygen and glucose deprivation (OGD) was performed to simulate ischemia in H9c2 cardiomyocytes.
Bioinformatics analysis revealed that the key targets of ginkgetin for MI treatment were MMP2, MMP9, and VEGFA. Immune infiltration analysis revealed that ginkgetin might be involved in immune regulation by acting on the TCR signaling pathway. The results of the GO enrichment analysis revealed that ginkgetin might protect the heart by acting on the cell membrane to alleviate the senescent apoptosis of cardiomyocytes after MI. In vivo studies revealed that ginkgetin ameliorated myocardial pathological damage and cardiac decompensation after MI. It also alleviated the inflammatory infiltration and senescent apoptosis of cardiomyocytes after MI. Additionally, ginkgetin can downregulate the activation signals of the TCR signaling pathway by dephosphorylating CD3 and CD28. In vitro studies revealed that ginkgetin attenuated elevated OGD-induced cytotoxicity, increased cell viability, and alleviated OGD-induced senescent apoptosis, thus protecting cardiomyocytes.
Ginkgetin inhibits postinfarction myocardial fibrosis and cardiomyocyte hypertrophy, scavenges oxygen free radicals, decreases postinfarction limbic cell inflammatory infiltration, suppresses activation of the inflammatory-immune pathway, and delays postinfarction peripheral cells from undergoing senescent apoptosis, thus protecting the heart.
心肌梗死（MI）是一种影响全球个体的常见心血管疾病。需要确定更有效的治疗药物，以尽量减少心肌细胞损伤并增强心脏保护作用。银杏提取物被广泛用于治疗神经系统疾病和外周血管疾病。本研究的目的是通过生物信息学和实验验证来确定银杏黄素对梗死后心肌细胞的保护作用及机制。
进行生物信息学分析以预测银杏黄素治疗MI的潜在生物学机制。接下来，我们通过实验进行进一步验证。对于体内研究，我们采用冠状动脉结扎构建MI大鼠模型。在体外，进行氧糖剥夺（OGD）以模拟H9c2心肌细胞中的缺血。
生物信息学分析显示，银杏黄素治疗MI的关键靶点是基质金属蛋白酶2（MMP2）、基质金属蛋白酶9（MMP9）和血管内皮生长因子A（VEGFA）。免疫浸润分析显示，银杏黄素可能通过作用于T细胞受体（TCR）信号通路参与免疫调节。基因本体（GO）富集分析结果显示，银杏黄素可能通过作用于细胞膜来保护心脏，以减轻MI后心肌细胞的衰老凋亡。体内研究显示，银杏黄素改善了MI后的心肌病理损伤和心脏失代偿。它还减轻了MI后心肌细胞的炎症浸润和衰老凋亡。此外，银杏黄素可通过使CD3和CD28去磷酸化来下调TCR信号通路的激活信号。体外研究显示，银杏黄素减轻了OGD诱导的细胞毒性升高，增加了细胞活力，并减轻了OGD诱导的衰老凋亡，从而保护心肌细胞。
银杏黄素抑制梗死后心肌纤维化和心肌细胞肥大，清除氧自由基，减少梗死后边缘区细胞炎症浸润，抑制炎症免疫途径的激活，并延缓梗死后外周细胞衰老凋亡，从而保护心脏。
