A Quantitative Serum Proteomic Analysis Helps to Explore the Comprehensive Mechanism and Identify Serum Biomarkers of Shengmai Injection's Effect on Isoproterenol-Induced Myocardial Ischemia in Rats

定量血清蛋白质组学分析有助于探索生脉注射液对异丙肾上腺素诱导的大鼠心肌缺血影响的综合机制和识别血清生物标志物

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作者:Xiaoping Zhang, Jie Zhang, Xiangyu Ji, Zhenzhen Wei, Baoyue Ding, Guoqiang Liu, Xiaoqing Lv, Yongxia Zheng, Shuyu Zhan

Abstract

Shengmai injection (SMI), a traditional Chinese medicine formula with the nature of multicomponent and multi-target, has been widely used in clinic for treating cardiovascular diseases in China; however, its comprehensive mechanism of action remains unclear. In this study, a TMT-based quantitative serum proteomics was performed to explore SMI's global mechanism and help identify serum biomarkers of its effect on isoproterenol (ISO)-induced myocardial ischemia rats. The results of TMT-based proteomic analysis identified 227, 100, and 228 differentially expressed proteins (DEPs) for the model compared to the control group, SMI pretreatment + model compared to the model group, and SMI pretreatment + model compared to the control group, respectively. Based on bioinformatics analyses of gene ontology (GO), KEGG pathways, and the protein-protein interaction (PPI) networks for the DEPs, it is concluded that the comprehensive mechanism of SMI's effect on ISO-induced myocardial ischemia injury includes regulation of energy metabolism, reducing endothelial cell permeability, regulation of vessel and cardiac contractility, anti-inflammation, and prevention of cell apoptosis. Furthermore, 10 common DEPs were found, and six of them were regulated in model vs. control group, while back-regulated in SMI pretreatment + model vs. model group. Among them, three functional proteins of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Fas apoptotic inhibitory molecule 3 (FAIM3), and uncharacterized protein (M0R5J4), which were verified by the PRM analysis, might be the potential serum biomarkers on SMI's effects. Overall, this serum proteomics of SMI not only provides insights into the comprehensive mechanism underlying SMI's effects on ischemic heart disease but also helps identify serum biomarkers for directing SMI's cardioprotective effects.

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