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一种新型化合物，丹参素冰片酯，通过mTOR/β-TrCP/NRF2途径抑制氧化应激来改善压力超负荷诱导的心肌肥厚。

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

作者信息

Han Dongjian, Wang Fuhang, Wang Bo, Qiao Zhentao, Cui Xinyue, Zhang Yi, Jiang Qingjiao, Liu Miaomiao, Shangguan Jiahong, Zheng Xiaohui, Bai Yajun, Du Chunyan, Shen Deliang

机构信息

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Pharmacol. 2022 Feb 3;13:830763. doi: 10.3389/fphar.2022.830763. eCollection 2022.

DOI:10.3389/fphar.2022.830763
PMID:35185583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8850779/
Abstract

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 and through nuclear NRF2 accumulation, and enhanced NRF2 stability regulating the mTOR/β-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.

摘要

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。在本研究中，我们研究了DBZ在氧化应激和内质网（ER）应激下对肥大心脏的治疗作用和潜在机制。使用主动脉缩窄（TAC）手术在大鼠中建立肥大模型，并使用血管紧张素II（Ang II）在新生大鼠心肌细胞（NRCMs）中建立肥大模型。我们的结果表明，DBZ显著抑制氧化应激和ER应激，阻断自噬流，减少细胞凋亡，并通过核NRF2积累增强NRF2稳定性，调节mTOR/β-TrcP/NRF2信号通路。因此，DBZ可能是应激诱导的心脏肥大的一种有前景的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/2ec680416d11/fphar-13-830763-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/138442937dd9/fphar-13-830763-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/f3212b55ae1f/fphar-13-830763-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/2a1169dc1a2f/fphar-13-830763-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/71fe0960fef9/fphar-13-830763-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/559ac9193d25/fphar-13-830763-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/e695491efade/fphar-13-830763-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/2ec680416d11/fphar-13-830763-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/138442937dd9/fphar-13-830763-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/3735f3f9ab06/fphar-13-830763-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/f3212b55ae1f/fphar-13-830763-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/cdce8095af53/fphar-13-830763-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/3515675e1512/fphar-13-830763-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/2a1169dc1a2f/fphar-13-830763-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/71fe0960fef9/fphar-13-830763-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/559ac9193d25/fphar-13-830763-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/e695491efade/fphar-13-830763-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d00f/8850779/2ec680416d11/fphar-13-830763-g009.jpg

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