Decoding the key targets and signal pathways in the regulation of myocardial infarction microenvironment by BSHYSXD based on molecular docking technology/network pharmacology. Decoding the key targets and signal pathways in the regulation of myocardial infarction microenvironment by BSHYSXD based on molecular docking technology/network pharmacology

Objective: To analyze the mechanism of Bushen Huayu Shengxin Decoction(BSHYSXD) in regulating ischemic and hypoxic microenvironment in the myocardial infarction area, and to identify key targets and signal pathways in the infarct microenvironment associated with promoting regeneration and repair of damaged tissue based on network pharmacology and molecular docking technology. Methods: LC-MS/MS technique was used to identify the drug-containing serum of BSHYSXD and determine the components entering into blood. The acute myocardial infarction model of rats was established by referring to the Olivette method. RNASeq technology, and network pharmacology combined with molecular docking technique were used to screen differentially expressed genes. GO enrichment analysis, KEGG pathway analysis, and RT-qPCR technology were used to identify the key targets and the reliability of key signal pathways. Results: The blood-containing components of BSHYSXD were baicalin, rubiadin, catalpol, Rehmapicrogenin, physcion, and ferulic acid. Among them, baicalin and rubiadin had the best docking effect with the targets with a strong correlation. The results of bioinformatics technology showed that the targets with a strong correlation with the infarcted area microenvironment were Egfr, Src, Ptgs2, Mmp9, Kdr, and the signal pathways were PI3K/Akt, HIF-1, VEGF, calcium channel, NF-kB, and so on. The results of the RT-PCR test showed that BSHYSXD could down-regulate the mRNA expression of Egfr, Src, NF-kB, PI3K, and AKT in myocardial ischemia and hypoxia microenvironment, and up-regulate the mRNA expression of Kdr. Conclusions: BSHYSXD may promote the regeneration and repair of myocardial injured tissue by regulating the key targets such as Egfr, Src, Kdr, and other key targets, and affecting the signal pathways such as PI3K/Akt and NF-kB.