Bai Jue, Yang Si-Yuan, Yu Shao-Mei, Cao Ying, Ma Chang-Han, Hu Xuan-Yi, Chen Xiong, Song Ying-Nan, Chen Hong-Jin
Translational Medicine Research Center, Guizhou Medical University, Guiyang, Guizhou, China.
Division of cardiac surgery, Guizhou Institute of Precision Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Front Pharmacol. 2025 Apr 29;16:1544869. doi: 10.3389/fphar.2025.1544869. eCollection 2025.
Myocardial ischemia/reperfusion injury (MIRI) is a critical problem in cardiovascular medicine, often occurring after coronary revascularization procedures or cardiopulmonary bypass. The characters of MIRI are both energy metabolism disturbances and severe myocardium insulin resistance (IR), which exacerbated myocardial damage and cell death. Isoliquiritigenin (ISL), a flavonoid derived from licorice roots ( spp.), has demonstrated protective effects on MIRI. However, the potential cardio-protective effects and mechanism of ISL in MIRI remain unclear.
In this study, we aimed to investigate ISL's therapeutic effects on MIRI. Moreover, we elucidate the underlying mechanisms of ISL regulated myocardium insulin resistance and .
SD rats underwent left anterior descending coronary artery ligation/reperfusion to induce MIRI. Chest echocardiography was performed to monitor cardiac function post-reperfusion, followed by measurement of myocardial injury and IR markers. H9C2 cardiomyocytes subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Markers associated with myocardial injury and IR were assessed. Then, we identified potential therapeutic targets IGFBP5 for MIRI by network pharmacology and molecular docking analysis. Finally, lentivirus were used to silence or over-express IGFBP5 to elucidate the role of IGFBP5 in regulating the therapeutic effects of ISL on IR in MIRI.
In the present study, experiments demonstrated that ISL attenuated myocardial infarct size, decreased serum markers of myocardial injury, improved left ventricular systolic function, and enhanced insulin sensitivity. data revealed that ISL ameliorated glucose uptake and cell survival rate. Furthermore, ISL increased AKT phosphorylation and upregulated membrane-bound GLUT4 (M-GLUT4) protein expression levels. These effects of ISL are mediated by the induction of IGFBP5, as demonstrated using gene-specific shRNA or overexpression for IGFBP5.
Our results reveal that ISL protects against myocardial damage caused by MIRI through the regulation of IR via the IGFBP5/AKT/GLUT4 pathway.
心肌缺血/再灌注损伤（MIRI）是心血管医学中的一个关键问题，常发生于冠状动脉血运重建术或体外循环后。MIRI的特征是能量代谢紊乱和严重的心肌胰岛素抵抗（IR），这会加剧心肌损伤和细胞死亡。异甘草素（ISL）是一种从甘草根中提取的黄酮类化合物，已证明对MIRI具有保护作用。然而，ISL在MIRI中的潜在心脏保护作用及机制仍不清楚。
在本研究中，我们旨在探究ISL对MIRI的治疗作用。此外，我们阐明ISL调节心肌胰岛素抵抗的潜在机制。
对SD大鼠进行左冠状动脉前降支结扎/再灌注以诱导MIRI。再灌注后进行胸部超声心动图检查以监测心脏功能，随后测量心肌损伤和IR标志物。对H9C2心肌细胞进行氧糖剥夺/再灌注（OGD/R）。评估与心肌损伤和IR相关的标志物。然后，我们通过网络药理学和分子对接分析确定MIRI的潜在治疗靶点IGFBP5。最后，使用慢病毒沉默或过表达IGFBP5，以阐明IGFBP5在调节ISL对MIRI中IR的治疗作用中的作用。
在本研究中，实验表明ISL可减小心肌梗死面积，降低心肌损伤血清标志物，改善左心室收缩功能，并增强胰岛素敏感性。数据显示ISL改善了葡萄糖摄取和细胞存活率。此外，ISL增加了AKT磷酸化并上调了膜结合型GLUT4（M-GLUT4）蛋白表达水平。如使用针对IGFBP5的基因特异性shRNA或过表达所证明的，ISL的这些作用是由IGFBP5的诱导介导的。
我们的结果表明，ISL通过IGFBP5/AKT/GLUT4途径调节IR，从而保护免受MIRI引起的心肌损伤。
