Deng Wei, Fang Yi, Liu Yuan, Zhou Heng, Cheng Zhihong, Zhang Yang, Sun Di, He Mengying, Lin Yafen, Zhang Rui, Zhang Jieyu, Li Wei, Tang Qizhu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
National Pharmaceutical Engineering Research Center, Shanghai 201203, P.R. China.
Mol Med Rep. 2014 Jul;10(1):211-6. doi: 10.3892/mmr.2014.2206. Epub 2014 May 2.
Cardiac remodeling is a major determinant of heart failure characterized by cardiac hypertrophy and fibrosis. Sanguinarine exerts widespread pharmacological effects, including antitumor and anti‑inflammatory responses. In the present study, the effect of sanguinarine on cardiac hypertrophy, fibrosis and heart function was determined using the model induced by aortic banding (AB) in mice. AB surgery and sham surgery were performed on male wild‑type C57 mice, aged 8‑10 weeks, with or without administration of sanguinarine from one week after surgery for an additional seven weeks. Sanguinarine protected against the cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by the heart weight/body weight, lung weight/body weight and heart weight/tibia length ratios, echocardiographic and hemodynamic parameters, histological analysis, and the gene expression levels of hypertrophic and fibrotic markers. The inhibitory effect of sanguinarine on cardiac remodeling was mediated by inhibiting nuclear factor (NF)‑κB signaling pathway activation. The findings indicated that sanguinarine protected against cardiac hypertrophy and fibrosis via inhibiting NF‑κB activation. These findings may be used to develop a potential therapeutic drug for treating cardiac remodeling and heart failure.
心脏重塑是以心肌肥厚和纤维化特征的心力衰竭的主要决定因素。血根碱具有广泛的药理作用,包括抗肿瘤和抗炎反应。在本研究中,使用小鼠主动脉缩窄(AB)诱导的模型确定血根碱对心肌肥厚、纤维化和心脏功能的影响。对8至10周龄的雄性野生型C57小鼠进行AB手术和假手术,术后一周开始给予或不给予血根碱,持续额外7周。通过心脏重量/体重、肺重量/体重和心脏重量/胫骨长度比值、超声心动图和血流动力学参数、组织学分析以及肥厚和纤维化标志物的基因表达水平评估,血根碱可预防AB诱导的心肌肥厚、纤维化和功能障碍。血根碱对心脏重塑的抑制作用是通过抑制核因子(NF)-κB信号通路激活介导的。这些发现表明,血根碱通过抑制NF-κB激活来预防心肌肥厚和纤维化。这些发现可用于开发一种治疗心脏重塑和心力衰竭的潜在治疗药物。