Wang Mingzhu, Shi Yanan, Yao Lei, Li Qiang, Wang Youhua, Li Jianhua, Fu Deyu
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Front Pharmacol. 2020 Jun 24;11:957. doi: 10.3389/fphar.2020.00957. eCollection 2020.
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.
越来越多的证据表明，黄芪甲苷IV（AS-IV）可改善心脏功能并保护心血管系统。然而，其涉及的分子靶点仍不明确。在本研究中，我们报告了相关研究，表明AS-IV可拮抗斑马鱼的心律失常，并减轻乌头碱诱导的心脏损伤。斑马鱼在研究药物对心血管疾病的影响方面具有一定优势。我们分析了其中可能涉及的机制，并预测了关键基因靶点。首先，建立了乌头碱诱导的心脏损伤模型，然后筛选出AS-IV的安全药物浓度，并在安全药物浓度范围内选择合适的药物剂量梯度。其次，通过观察斑马鱼心率以及心脏和血管结构的变化，证实了AS-IV在心血管系统中的保护作用。第三，我们旨在通过RNA测序检测差异表达基因（DEG），来阐明AS-IV对斑马鱼心率和乌头碱诱导的心脏损伤的拮抗机制。然后，通过生物信息学技术，如功能富集分析、蛋白质-蛋白质相互作用网络和DNA-微小RNA网络等，对DEG进行进一步分析。接下来，我们预测了AS-IV心脏保护作用的关键基因。最后，我们在不同的心脏损伤转录组序列数据集中验证了这些基因。因此，我们得出结论，miR-26b-5p/ATF3/JUN是AS-IV的关键靶点，在维持心脏稳态和调节心脏重塑中发挥重要作用。
