Zhang Mu-Xin, Huang Xue-Ying, Song Yu, Xu Wan-Li, Li Yun-Lun, Li Chao
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Pharmacol. 2023 Jan 9;13:1103557. doi: 10.3389/fphar.2022.1103557. eCollection 2022.
Schischkin and Bunge (AS) have been clinically used as adjunctive drugs in the treatment of myocardial ischemia (MI). However, the effect and mechanism of AS on MI have yet to be fully recognized. Here, we explored the cardioprotective effect of their combined use, and the mechanism of promoting angiogenesis through pericyte recruitment. Our data revealed that AS reduced MI and protects cardiac function. AS-treated MI mice exhibited reduced ST-segment displacement and repolarization time, increased ejection fraction, and less BNP and NT-proBNP expression. Pathological studies showed that, AS reduced the area of infarcted myocardium and slowed down the progress of cardiac remodelling and fibrosis. In addition, AS increased the content of platelet-derived growth factor receptors β (PDGFR-β), platelet endothelial cell adhesion molecule-1 (CD31) and angiogenesis-related proteins including vascular endothelial cadherin (VE-cadherin), Vascular Endothelial Growth Factor (VEGF) and transforming growth factor β (TGF-β). Moreover, these botanical drugs upregulated the expression of Angiopoietin-1 (Ang-1), phosphorylated angiopoietin-1 receptor (p-Tie-2), focal adhesion kinase (FAK) and growth factor receptor bound protein 7 (GRB7), indicating that the cardioprotection-related angiogenesis effect was related to pericyte recruitment, which may be through Ang-1/Tie-2/FAK pathway. In summary, AS can treat MI by protecting cardiac function, attenuating cardiac pathological changes, and hindering the progression of heart failure, which is related to angiogenesis after pericyte recruitment. Therefore, AS at a certain dose can be a promising treatment for MI with broad application prospects.
Schischkin和Bunge（AS）已在临床上用作治疗心肌缺血（MI）的辅助药物。然而，AS对MI的作用和机制尚未得到充分认识。在此，我们探讨了它们联合使用的心脏保护作用，以及通过周细胞募集促进血管生成的机制。我们的数据显示，AS可减轻MI并保护心脏功能。经AS治疗的MI小鼠表现出ST段位移和复极时间减少、射血分数增加，以及BNP和NT-proBNP表达减少。病理研究表明，AS减少了梗死心肌面积，减缓了心脏重塑和纤维化的进程。此外，AS增加了血小板衍生生长因子受体β（PDGFR-β）、血小板内皮细胞黏附分子-1（CD31）以及包括血管内皮钙黏蛋白（VE-钙黏蛋白）、血管内皮生长因子（VEGF）和转化生长因子β（TGF-β）在内的血管生成相关蛋白的含量。此外，这些植物药上调了血管生成素-1（Ang-1）、磷酸化血管生成素-1受体（p-Tie-2）、黏着斑激酶（FAK）和生长因子受体结合蛋白7（GRB7）的表达，表明心脏保护相关的血管生成作用与周细胞募集有关，这可能是通过Ang-1/Tie-2/FAK途径实现的。总之，AS可通过保护心脏功能、减轻心脏病理变化以及阻碍心力衰竭的进展来治疗MI，这与周细胞募集后的血管生成有关。因此，一定剂量的AS有望成为治疗MI的药物，具有广阔的应用前景。
