Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy.
Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy.
复制标题
槐苷通过激活 AMPK/mTORC1 介导的自噬来改善心脏肥大。
DOI：
10.1042/bsr20200661
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发表时间：
2020-11-27
影响因子：
4
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Gao M;Hu F;Hu M;Hu Y;Shi H;Zhao GJ;Jian C;Ji YX;Zhang XJ;She ZG;Li H;Zhu L
目的：评价苦参皂苷(SOP)对心肌肥厚的保护作用。同时，应拓宽其潜力和意义，使其成为治疗病理性心肌肥厚和心力衰竭的有吸引力的药物。方法：采用苯肾上腺素(PE)诱导的新生大鼠心肌细胞(NRCM)扩大模型，观察SOP对心肌细胞扩大的保护作用。在接受横断性主动脉缩窄(TAC)或假手术的小鼠上验证SOP的功能。TAC术后1周给予SOP治疗4周，超声心动图检查后取心。结果：SOP可显著减轻TAC诱导的心功能不全、心肌细胞肥大和心肌纤维化。在机制上，Sop处理可显著激活持续肥大刺激后的AMPK/mTORC1-自噬级联反应。重要的是，Sop的保护作用可被AMPKα抑制剂化合物C基本消除，提示Sop功能的AMPK激活依赖方式抑制病理性心肌肥厚。结论：SOP通过激活AMPK/mTORC1介导的自噬机制减轻心肌肥厚。因此，SOP可能是治疗病理性心肌肥厚和心力衰竭的有吸引力的候选药物。
Aim: The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure. Methods: Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination. Results: Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy. Conclusion: Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.