School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Biomed Pharmacother. 2019 Apr;112:108599. doi: 10.1016/j.biopha.2019.108599. Epub 2019 Feb 21.
Heart failure (HF) leads to an increase in morbidity and mortality globally. Tanshinone IIA is an important traditional Chinese medicine monomer and has been shown to have remarkable protective effect against HF. Autophagy is critically involved in the progression of HF. The effect of Tanshinone IIA on autophagy has not been clarified yet. In this study, left anterior descending (LAD) ligation was used to induce HF model and a hydrogen peroxide-(HO-)-induced H9C2 cell injury model was established. in vivo, echocardiography results showed that Tanshinone IIA could significantly improve heart function. Western Blot result showed that Tanshinone IIA treatment enhanced autophagy and regulated expressions of key autophagy-related molecules, including protein 1 light chain 3 (LC3), p62 and Beclin1. Tanshinone IIA also inhibited apoptosis and regulated expressions of key apoptotic protein, including B cell lymphoma-2 (Bcl-2) and Bcl-2 Associated X Protein (Bax) and cleaved caspase-3 and -7. Further experiments demonstrated that the effects of Tanshinone IIA were mediated through upregulation of AMP-activated protein kinase (AMPK) and downregulation of mammalian target of rapamycin (mTOR) simultaneously. The mTOR agonist MHY1485 could abrogate the therapeutic effect of Tanshinone IIA in vitro. In conclusion, Tanshinone IIA protects cardiomyocytes and improves cardiac function by inhibiting apoptosis and inducing autophagy via activation of the AMPK-mTOR signaling pathway.
心力衰竭（HF）导致全球发病率和死亡率增加。丹参酮 IIA 是一种重要的中药单体，已被证明对 HF 具有显著的保护作用。自噬在 HF 的进展中起着至关重要的作用。丹参酮 IIA 对自噬的影响尚未阐明。在这项研究中，使用左前降支（LAD）结扎诱导 HF 模型，并建立了过氧化氢（HO-）诱导的 H9C2 细胞损伤模型。在体内，超声心动图结果表明丹参酮 IIA 可显著改善心脏功能。Western blot 结果表明，丹参酮 IIA 处理可增强自噬并调节关键自噬相关分子的表达，包括蛋白 1 轻链 3（LC3）、p62 和 Beclin1。丹参酮 IIA 还抑制凋亡并调节关键凋亡蛋白的表达，包括 B 细胞淋巴瘤-2（Bcl-2）和 Bcl-2 相关 X 蛋白（Bax）以及裂解的 caspase-3 和 -7。进一步的实验表明，丹参酮 IIA 的作用是通过同时上调 AMP 激活的蛋白激酶（AMPK）和下调哺乳动物雷帕霉素靶蛋白（mTOR）介导的。mTOR 激动剂 MHY1485 可消除丹参酮 IIA 在体外的治疗作用。总之，丹参酮 IIA 通过激活 AMPK-mTOR 信号通路抑制凋亡和诱导自噬来保护心肌细胞并改善心脏功能。
