AUTHOR=Wang Mingzhu , Shi Yanan , Yao Lei , Li Qiang , Wang Youhua , Li Jianhua , Fu Deyu TITLE=Identification of Hub Genes in Protective Effect of Astragaloside IV on Aconitine-Induced Cardiac Damage in Zebrafish Based on Bioinformatics Analysis JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00957 DOI=10.3389/fphar.2020.00957 ISSN=1663-9812 ABSTRACT=

Accumulating evidence suggests that Astragaloside IV (AS-IV) improves cardiac function and protects the cardiovascular system. However, the molecular targets involved remain ambiguous. In this work, we report research suggesting that AS-IV can antagonize arrhythmias and reduce the cardiac damage induced by aconitine in zebrafish. Zebrafish have certain benefits with respect to studying the effect of drugs on cardiovascular disease. The possible mechanisms involved are analyzed, and hub gene targets are predicted. First, a model of cardiac damage induced by aconitine was created, and then a safe drug concentration of AS-IV was screened, and the appropriate drug dose gradient was selected within a safe drug concentration range. Second, we confirmed the protective effect of AS-IV in the cardiovascular system by observing changes in zebrafish heart rates and the cardiac and vascular structure. Third, we aimed to demonstrate the antagonistic mechanism of AS-IV on heart rate and cardiac damage induced by aconitine in zebrafish, with differentially expressed genes (DEGs) detected by RNA sequencing. The DEGs were then further analyzed by bioinformatic techniques, such as function enrichment analysis, protein-protein interaction network, and DNA-microRNA networks, for example. Next, we predicted the hub genes of the cardiac protective effects of AS-IV. Finally, we validated these genes in different transcriptome sequence datasets of cardiac damage. Thus, we conclude that miR-26b-5p/ATF3/JUN are key targets of AS-IV and play an important role in maintaining cardiac homeostasis and regulating cardiac remodeling.