Chang Jin-Jin, Xu Li-Xia, Yi Wen-Jing, Zhang Huan-Huan, Zhang Jun-Wei, Zheng Bin, Fu Ping-Ying, He Rui-Lan, Wang Rui-Xing, Jiang Jian-Feng, Gui Long-Xin, Wu Min-Xia, Lin Jun-Jin, Huang Zhi-Hong, Song Jia-Lin, Lin Mo-Jun, Jiao Hai-Xia, Wu Zhi-Juan
The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
Department of Physiology and Pathophysiology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
J Ginseng Res. 2025 Sep;49(5):585-593. doi: 10.1016/j.jgr.2025.06.003. Epub 2025 Jun 30.
Myocardial hypertrophy is a crucial pathological change that occurs during post-anthracycline treatment cardiomyopathy. The effects of ginsenoside Rb1 (Rb1) on anthracycline-induced hypertrophy remain unclear. This study aimed to explore the antihypertrophic effect of Rb1 on post-doxorubicin (DOX) treatment myocardial hypertrophy and underlying mechanism.
Post-DOX treatment myocardial hypertrophy was induced 12 days or 22 h after 15 mg/kg DOX injection in C57BL/6 mice or 2 h DOX (2 μM) incubation in H9c2 cardiomyoblasts. Rb1 was administered 2 days before DOX exposure for 14 consecutive days or 6 h before DOX incubation for 30 h. Heart weight/Body weight (HW/BW), heart weight/tibia length (HW/TL) ratios, echocardiography, WGA staining and the contents of α-SMA, BNP and β-MCH were used to validate myocardial hypertrophy. HE staining, Masson staining, and transmission electron microscopy were performed to assess changes in cardiac morphology. Fluo-3/AM fluorescence was applied to measure the cytosolic free calcium concentration. Western blot, immunohistochemical and immunofluorescence staining were used to assess the expression of CaNBβ/NFATc4/GATA4 signaling.
Rb1 significantly decreased the HW/BW, HW/TL and LVd mass/BW ratios, reduced the cardiomyocyte area and the expression of BNP, β-MHC and α-SMA. Rb1 also relieved myocardial fibrosis and subcellar structure changes and improved the cardiac hemodynamics of post-DOX treatment mice. Rb1 decreased post-DOX treatment calcium overload. Consistent with these findings, and CaN, NFATc4 and GATA4 overexpression was rectified.
Rb1 ameliorated post-doxorubicin treatment myocardial hypertrophy, which may be correlated with CaN/NFAT/GATA4 downregulation.
心肌肥大是蒽环类药物治疗后心肌病发生过程中的关键病理变化。人参皂苷Rb1（Rb1）对蒽环类药物诱导的肥大的影响尚不清楚。本研究旨在探讨Rb1对多柔比星（DOX）治疗后心肌肥大的抗肥大作用及其潜在机制。
在C57BL/6小鼠中注射15mg/kg DOX后12天或22小时，或在H9c2心肌成纤维细胞中孵育2小时DOX（2μM），诱导DOX治疗后心肌肥大。在DOX暴露前2天连续给药14天给予Rb1，或在DOX孵育前6小时给药30小时。采用心脏重量/体重（HW/BW）、心脏重量/胫骨长度（HW/TL）比值、超声心动图、WGA染色以及α-SMA、BNP和β-MCH的含量来验证心肌肥大。进行HE染色、Masson染色和透射电子显微镜检查以评估心脏形态的变化。应用Fluo-3/AM荧光法测量胞质游离钙浓度。采用蛋白质免疫印迹法、免疫组织化学和免疫荧光染色法评估CaNBβ/NFATc4/GATA4信号通路的表达。
Rb1显著降低了HW/BW、HW/TL和左心室质量/体重比值，减少了心肌细胞面积以及BNP、β-MHC和α-SMA的表达。Rb1还减轻了心肌纤维化和亚细胞结构变化，并改善了DOX治疗后小鼠的心脏血流动力学。Rb1降低了DOX治疗后的钙超载。与这些发现一致，CaN、NFATc4和GATA4的过表达得到纠正。
Rb1改善了多柔比星治疗后的心肌肥大，这可能与CaN/NFAT/GATA4的下调有关。
