脑心通胶囊抗心肌梗死的血清蛋白质组学研究

Serum proteomics study of Naoxintong Capsule against myocardial infarction

关键词:  脑心通胶囊  血清蛋白质组学  心肌梗死  血管生成  细胞凋亡

Key words:  Naoxintong Capsule  serum proteomics  myocardial infarction  angiogenesis  apoptosis

摘要:

[目的] 基于血清蛋白质组学探讨脑心通胶囊抗心肌梗死（MI）的可能作用机制。[方法] 采用左冠状动脉前降支结扎法建立C57BL/6小鼠MI模型，脑心通组予以300 mg/（kg·d）灌胃3 d。通过双向凝胶电泳（2-DE）联合基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）筛选差异表达蛋白（DEPs），蛋白免疫印迹（Western blot）法验证关键靶点，蛋白芯片检测血管生成相关因子。[结果] 脑心通可以减少左心室梗死面积，降低心肌细胞凋亡率。筛选出100个差异表达蛋白（DEPs），其中血管生成抑制蛋白1（Vash1）、甘油-3-磷酸脱氢酶1（Gpd1）、组织金属蛋白酶抑制剂3（Timp3）、线粒体融合蛋白1（Mfn1）等蛋白表达显著变化。脑心通上调血小板衍生生长因子-BB（PDGF-BB）表达，激活蛋白激酶B（Akt）/内皮型一氧化氮合酶（eNOS）通路。[结论] 脑心通胶囊通过协同调控Vash1/PDGF-BB介导的血管生成、Timp3/基质金属蛋白酶9（MMP9）主导的基质重塑及Mfn1依赖的线粒体动力学三重网络发挥心肌保护效应。

Abstract:

[Objective] To investigate the mechanism of Naoxintong capsule against myocardial infarction（MI） through serum proteomics. [Methods] MI was induced by ligating the left anterior descending coronary artery in C57BL/6 mice. Naoxintong[300 mg/（kg·d）]was administered for 3 days. Differentially expressed proteins（DEPs） were screened by two-dimensional gel electrophoresis（2-DE） and Matrix assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry（MALDI-TOF-MS），validated by Western blot. Angiogenesis-related proteins were analyzed using proteomic arrays. [Results] Naoxintong reduced left ventricular infarct size and decreased cardiomyocyte apoptosis. Proteomic analysis identified 100 DEPs，including Vash1，Gpd1，Timp3，and Mfn1. Naoxintong upregulated PDGF-BB expression and activated the Akt/eNOS pathway. [Conclusion] Naoxintong exerts myocardial protective effects by synergistically regulating a triple network involving Vash1/PDGF-BB-mediated angiogenesis，TIMP3/MMP9-dominated matrix remodeling，and Mfn1-dependent mitochondrial dynamics.