Zhou Qiaofeng, Jiang Na, Li Shihuan, Li Suqin, Liu Jie, Yu Liangzhu, Liu Guoli, Xia Hongli, Li Mincai
Hubei Key Laboratory of Diabetes and Angiopathy, Xianning, 437100, P.R. China.
School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, P.R. China.
J Cardiovasc Transl Res. 2025 Aug 27. doi: 10.1007/s12265-025-10679-y.
Myocardial fibrosis (MF) severely impairs the heart structure and function post-myocardial infarction. The study investigated the effectiveness and mechanism of diammonium glycyrrhizinate (DG) on ISO-induced MF. ISO-stimulated mouse cardiac fibroblasts (CFs) were treated with DG to assess the proliferation, inflammation, and fibrosis markers (α-SMA, collagen, TGF-β1, Smad3). The MF model was induced in mice by administering ISO, followed by a 4-week treatment with DG (60 mg/kg/day). Cardiac function was measured using echocardiography, and histology and molecular analyses were performed. DG significantly suppressed the CF proliferation and reduced the expression of fibrotic markers. In ISO-treated mice, DG improved the cardiac function and attenuated the upregulated fibrosis markers. Molecular analysis revealed DG suppressed the TGF-β1/Smad3 pathway activation. The antifibrotic effect was enhanced when combined with STAT3 inhibition. DG effectively alleviates ISO-induced myocardial fibrosis dysfunction by inhibiting the STAT3/Smad3 signaling pathway, demonstrating its potential as a treatment for cardiac fibrosis.
心肌纤维化（MF）严重损害心肌梗死后的心脏结构和功能。本研究探讨了甘草酸二铵（DG）对异丙肾上腺素（ISO）诱导的MF的有效性及作用机制。用DG处理ISO刺激的小鼠心脏成纤维细胞（CFs），以评估细胞增殖、炎症和纤维化标志物（α-平滑肌肌动蛋白、胶原蛋白、转化生长因子-β1、Smad3）。通过给予ISO诱导小鼠MF模型，随后用DG（60mg/kg/天）进行4周治疗。采用超声心动图测量心功能，并进行组织学和分子分析。DG显著抑制CFs增殖，并降低纤维化标志物的表达。在ISO处理的小鼠中，DG改善了心功能，并减弱了上调的纤维化标志物。分子分析显示DG抑制了转化生长因子-β1/Smad3信号通路的激活。与抑制信号转导和转录激活因子3（STAT3）联合使用时，抗纤维化作用增强。DG通过抑制STAT3/Smad3信号通路有效减轻ISO诱导的心肌纤维化功能障碍，证明其作为心脏纤维化治疗药物的潜力。
