Wu Qing Q, Ni Jian, Zhang Ning, Liao Hai H, Tang Qi Z, Deng Wei
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Cardiovascular Research Institute, Wuhan University, Wuhan, China.
Front Pharmacol. 2017 Nov 14;8:808. doi: 10.3389/fphar.2017.00808. eCollection 2017.
Despite therapeutic advances, heart failure-related mortality rates remain high. Therefore, understanding the pathophysiological mechanisms involved in the remodeling process is crucial for the development of new therapeutic strategies. Andrographolide (Andr), a botanical compound, has potent cardio-protective effects due to its ability to inhibit mitogen-activated protein kinases (MAPKs). Andr has also been shown to inhibit inflammation and apoptosis, which are factors related to cardiac hypertrophy. Our aim was to evaluate the effects of Andr on cardiac hypertrophy and MAPKs activation. Thus, mice were subjected to aortic banding (AB) with/without Andr administration (25 mg/kg/day, orally). Cardiac function was accessed by echocardiography and hemodynamic parameters. Our results showed that Andr administration for 7 weeks decreased cardiac dysfunction and attenuated cardiac hypertrophy and fibrosis in AB mice. Andr treatment induced a strong reduction in the transcription of both hypertrophy (ANP, BNP, and β-MHC) and fibrosis related genes (collagen I, collagen III, CTGF, and TGFβ). In addition, cardiomyocytes treated with Andr showed a reduced hypertrophic response to angiotensin II. Andr significantly inhibited MAPKs activation in both mouse hearts and cardiomyocytes. Treatment with a combination of MAPKs activators abolished the protective effects of Andr in cardiomyocytes. Furthermore, we found that Andr also inhibited the activation of cardiac fibroblasts via the MAPKs pathway, which was confirmed by the application of MAPKs inhibitors. In conclusion, Andr was found to confer a protective effect against experimental cardiac hypertrophy in mice, suggesting its potential as a novel therapeutic drug for pathological cardiac hypertrophy.
尽管治疗取得了进展，但心力衰竭相关的死亡率仍然很高。因此，了解重塑过程中涉及的病理生理机制对于开发新的治疗策略至关重要。穿心莲内酯（Andr）是一种植物化合物，因其能够抑制丝裂原活化蛋白激酶（MAPK）而具有强大的心脏保护作用。Andr还被证明可以抑制炎症和细胞凋亡，而炎症和细胞凋亡是与心肌肥大相关的因素。我们的目的是评估Andr对心肌肥大和MAPK激活的影响。因此，对小鼠进行主动脉缩窄（AB）手术，并给予/不给予Andr（25mg/kg/天，口服）。通过超声心动图和血流动力学参数评估心脏功能。我们的结果表明，给予Andr 7周可降低AB小鼠的心脏功能障碍，减轻心肌肥大和纤维化。Andr治疗导致肥大相关基因（心钠素、脑钠肽和β-肌球蛋白重链）和纤维化相关基因（I型胶原、III型胶原、结缔组织生长因子和转化生长因子β）的转录显著降低。此外，用Andr处理的心肌细胞对血管紧张素II的肥大反应降低。Andr显著抑制小鼠心脏和心肌细胞中MAPK的激活。用MAPK激活剂联合处理消除了Andr对心肌细胞的保护作用。此外，我们发现Andr还通过MAPK途径抑制心脏成纤维细胞的激活，这一点通过应用MAPK抑制剂得到了证实。总之，发现Andr对小鼠实验性心肌肥大具有保护作用，表明其作为病理性心肌肥大新型治疗药物的潜力。
