He Yue, Dai Meng-Shi, Tao Li-Yu, Gu Xinsheng, Wang Hao, Liu Ping
Shanghai University of Traditional Chinese Medicine, Shanghai Eighth People's Hospital, Shanghai, China.
Department of Geriatrics, Huashan Hospital, Fudan University, Shanghai, China.
J Gene Med. 2025 Jan;27(1):e70003. doi: 10.1002/jgm.70003.
Cardiac dysfunction and adverse consequences induced by cardiac fibrosis have been well documented. However, the cardiac fibrosis pathway in chronic heart failure (CHF) remains unclear, and it is therefore necessary to conduct further research for the sake of developing more effective therapeutic strategies for CHF. Some recent studies suggest that Pericarpium Trichosanthis (PT) may help improve the progression of fibrotic diseases. To validate this possibility, we conducted an experiment to evaluate the effect of PT on cardiac fibrosis and explore the hidden mechanism. In the experiment, we induced cardiac fibrosis in rats by left anterior descending (LAD) coronary artery ligation. The findings revealed that PT reduced myocardial fibrosis and increased cardiac activity in CHF rats receiving LAD ligation. In addition, the TGF-β1 level was decreased, and the miR-29b expression was increased in CHF rats after PT treatment. Our in vitro experiment also demonstrated that PT treatment suppressed fibroblast activation and collagen synthesis in cardiac fibroblasts stimulated by TGF-β1， and at the same time decreased the TGF-β1 level and increased the miR-29b expression. We further verified that this action was correlated with the TGF-β/Smad3 signaling pathway. We also observe that miR-29b could suppress the TGF-β1 expression, and the suppression of miR-29b weakened the anti-fibrotic effect of PT. This suggests that PT could cure cardiac fibrosis and dysfunction both in vitro and in vivo via the TGF-β/Smad3 signaling pathway, while miR-29b may participate in this action.
心脏纤维化所导致的心脏功能障碍和不良后果已有充分记载。然而，慢性心力衰竭（CHF）中的心脏纤维化途径仍不明确，因此有必要进行进一步研究，以开发更有效的CHF治疗策略。最近的一些研究表明，瓜蒌皮（PT）可能有助于改善纤维化疾病的进展。为了验证这种可能性，我们进行了一项实验，以评估PT对心脏纤维化的影响并探索其潜在机制。在实验中，我们通过左前降支（LAD）冠状动脉结扎诱导大鼠心脏纤维化。研究结果显示，PT可减轻接受LAD结扎的CHF大鼠的心肌纤维化并增强心脏活性。此外，PT治疗后，CHF大鼠的TGF-β1水平降低，miR-29b表达增加。我们的体外实验还表明，PT处理可抑制TGF-β1刺激的心脏成纤维细胞的成纤维细胞活化和胶原蛋白合成，同时降低TGF-β1水平并增加miR-29b表达。我们进一步证实，这种作用与TGF-β/Smad3信号通路相关。我们还观察到miR-29b可抑制TGF-β1表达，而抑制miR-29b会削弱PT的抗纤维化作用。这表明PT可通过TGF-β/Smad3信号通路在体外和体内治愈心脏纤维化和功能障碍，而miR-29b可能参与了这一作用。
