A Novel Compound, Tanshinol Borneol Ester, Ameliorates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Oxidative Stress via the mTOR/β-TrCP/NRF2 Pathway.

A Novel Compound, Tanshinol Borneol Ester, Ameliorates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Oxidative Stress via the mTOR/β-TrCP/NRF2 Pathway.
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一种新型化合物,丹参醇冰片酯,通过 mTOR/β-TrCP/NRF2 途径抑制氧化应激,改善压力过载引起的心脏肥大

DOI:
10.3389/fphar.2022.830763
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发表时间:
2022
影响因子:
5.6
通讯作者:
Shen D
Shen D
中科院分区:
医学2区
文献类型:
--
作者:
Han D;Wang F;Wang B;Qiao Z;Cui X;Zhang Y;Jiang Q;Liu M;Shangguan J;Zheng X;Bai Y;Du C;Shen D

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丹参醇冰片酯 (DBZ) 具有抗动脉粥样硬化和抗炎作用。然而,其对心脏肥大的影响尚不清楚。在这项工作中,我们研究了DBZ对氧化应激和内质网(ER)应激下肥厚心脏的治疗效果和潜在机制。使用横主动脉缩窄 (TAC) 手术在大鼠中建立肥厚模型,并使用血管紧张素 II (Ang II) 在新生大鼠心肌细胞 (NRCM) 中建立肥厚模型。我们的结果表明,DBZ 通过核 NRF2 积累显着抑制氧化应激和 ER 应激,阻断自噬流,减少体内和体外细胞凋亡,并通过调节 mTOR/β-TrcP/NRF2 信号通路增强 NRF2 稳定性。因此,DBZ 可能成为治疗应激性心脏肥大的一种有前途的治疗方法。
Tanshinol borneol ester (DBZ) exerts anti-atherosclerotic and anti-inflammatory effects. However, its effects on cardiac hypertrophy are not well understood. In this work, we investigated the treatment effects and potential mechanisms of DBZ on the hypertrophic heart under oxidative stress and endoplasmic reticulum (ER) stress. A hypertrophic model was established in rats using transverse-aortic constriction (TAC) surgery and in neonatal rat cardiomyocytes (NRCMs) using angiotensin II (Ang II). Our results revealed that DBZ remarkably inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis in vivo and in vitro through nuclear NRF2 accumulation, and enhanced NRF2 stability via regulating the mTOR/β-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.
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