Abstract：
Myocardial fibrosis (MF) is a pivotal pathological process implicated in various cardiovascular diseases, particularly heart failure. Astragaloside IV (AS-IV), a natural compound derived from Astragalus membranaceus, possesses potent cardioprotective properties. However, the precise molecular mechanisms underlying its anti-MF effects, particularly in relation to senescence, remain elusive. Thus, this study aimed to investigate the therapeutic potential and underlying molecular mechanisms of AS-IV in treating ISO-induced MF in mice, employing transcriptomics, proteomics, in vitro, and in vivo experiments. We assessed the positive effects of AS-IV on ISO-induced MF using HE staining, Masson staining, ELISA, immunohistochemical staining, transthoracic echocardiography, transmission electron microscopy, and DHE fluorescence staining. Additionally, we elucidated the regulatory role of AS-IV in MF through comprehensive transcriptomics and proteomics analyses, complemented by Western blotting and RT-qPCR validation of pertinent molecular pathways. Our findings demonstrated that AS-IV treatment markedly attenuated ISO-induced myocardial injury and oxidative stress, concomitantly inhibiting the release of SASPs. Furthermore, integrated transcriptomics and proteomics analyses revealed that the anti-MF mechanism of AS-IV was associated with regulating cellular senescence and the p53 signaling pathway. These results highlight AS-IV exerts its anti-MF effects not only by inhibiting oxidative stress but also by modulating senescence through the p53 signaling pathway.
摘要：
心肌纤维化(MF)是各种心血管疾病的重要病理过程,尤其是心力衰竭。黄芪甲苷（AS-IV），一种来自黄芪的天然化合物，具有有效的心脏保护特性。然而,其抗MF作用的精确分子机制，特别是关于衰老，仍然难以捉摸。因此，这项研究旨在探讨AS-IV治疗ISO诱导的MF小鼠的治疗潜力和潜在的分子机制，采用转录组学，蛋白质组学，在体外，和体内实验。我们使用HE染色评估了AS-IV对ISO诱导的MF的积极作用，Masson染色,ELISA,免疫组织化学染色，经胸超声心动图,透射电子显微镜,和DHE荧光染色。此外,我们通过全面的转录组学和蛋白质组学分析阐明了AS-IV在MF中的调节作用，通过Western印迹和RT-qPCR验证相关分子途径。我们的研究结果表明，AS-IV治疗可显着减轻ISO诱导的心肌损伤和氧化应激，同时抑制SASPs的释放。此外，整合转录组学和蛋白质组学分析显示AS-IV的抗MF机制与调节细胞衰老和p53信号通路有关。这些结果强调了AS-IV不仅通过抑制氧化应激而且通过p53信号通路调节衰老发挥其抗MF作用。
