Abstract: Objective To investigate the role and mechanism of Shuangshen Ningxin capsules (SSNXAIG) against myocardial infarction (MI) in mice via transcriptomics. Methods MI models were established in male C57BL/6J mice via cardiac compression combined with ligation of the left anterior descending artery (LAD). Mice were randomly divided into the sham group, MI model group, low dose of SSNXAIG (SSNXAIG-L) group, and high dose of SSNXAIG (SSNXAIG-H) group, with 9 in each group. The SSNXAIG-L group was given SSNXAIG suspension (0.125 g·kg^-1·d^-1), the SSNXAIG-H group received SSNXAIG suspension (0.250 g·kg^-1·d^-1), and the sham group and MI group were given double distilled water. Intragastric treatment lasted for 14 days. Cardiac indexes were measured. Cardiac function was assessed with Doppler ultrasound. Myocardial pathology was observed via HE staining while fibrosis was evaluated by Masson's trichrome staining. Differentially expressed genes (DEGs) were screened via RNA-seq, followed by GO annotation and KEGG enrichment analysis. Results Compared with the MI group, cardiac indexes were significantly reduced in the SSNXAIG-H group (P<0.01) while LVEF and LVFS were increased in SSNXAIG-L and SSNXAIG-H groups (P<0.01), and both doses mitigated myocardial injury, inflammatory infiltration and fibrosis. The transcriptome sequencing results showed that there were 2 243 DEGs (1 815 upregulated and 428 downregulated) in Sham and MI groups, 94 DEGs (13 upregulated and 81 downregulated) in MI and SSNXAIG groups, with 87 DEGs tending to be reversed. KEGG pathway analysis revealed that DEGs were primarily enriched in cell cycle, cellular senescence, and the p53 signaling pathway. Conclusion SSNXAIG can significantly reduce myocardial injury, improve cardiac function, and attenuate myocardial fibrosis in MI mice. The underlying mechanism may be associated with the modulation of cell cycle, cellular senescence, and the p53 signaling pathway.

Key words: Myocardial Infarction, Shuangshen Ningxin Capsule, Transcriptomics, Differentially Expressed Genes, Mice