Compound Danshen Tablets ameliorate myocardial ischemia/reperfusion injury-induced ventricular remodeling by regulating autophagy via AMPK/mTOR signaling pathway

IF 4.7 4区 医学 Q1 CHEMISTRY, MEDICINAL
Qiaoyu Li , Yun Luo , Haibiao Guo , Wenxiu Liu , Hui Yu , Chuyuan Li , Rongchang Chen , Xiaobo Sun
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引用次数: 0

Abstract

Objective

Left ventricular remodeling induced by myocardial ischemia/reperfusion injury (MI/RI) is a common cardiac dysfunction. Accumulating evidence has demonstrated that autophagy plays a vital role in protecting against ventricular remodeling. This study aims to investigate the performance of Compound Danshen Tablets (CDT) in rescuing ventricular remodeling and whether autophagy as the potential mechanism.

Methods

The left anterior descending arteries of rats were temporarily ligated for 30 min to construct the MI/RI model. Ventricular remodeling was induced by reperfusion for 28 d, during which the MI/RI rats were administered CDT (300 mg/kg and 600 mg/kg), atorvastatin (2 mg/kg), and diltiazem (16 mg/kg). Cardiac function and structure were examined by echocardiography. Immunohistochemistry, Masson's trichrome staining, and hematoxylin-eosin (HE) staining were utilized to assess the fibrosis and histological alterations in the heart tissue. The expression of autophagy-related proteins was detected using Western blotting.

Results

CDT attenuated the cardiac dysfunction, structural changes, histopathological changes and fibrosis induced by MI/RI. CDT significantly enhanced the level of Beclin1 and microtubule-associated protein 1 light chain 3 beta (LC3β), and reduced p62 levels in MI/RI rats. Moreover, CDT significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) phosphorylation.

Conclusion

CDT ameliorated MI/RI-induced ventricular remodeling by activating autophagy and improving autophagic flux via the AMPK/mTOR signaling pathway.
复方丹参片通过AMPK/mTOR信号通路调节自噬,改善心肌缺血再灌注损伤引起的心室重构
目的心肌缺血再灌注损伤(MI/RI)引起的左室重构是常见的心功能障碍。越来越多的证据表明,自噬在防止心室重构中起着至关重要的作用。本研究旨在探讨复方丹参片(CDT)对大鼠心室重构的修复作用及自噬是否为其潜在机制。方法暂时结扎大鼠左前降支30 min,建立心肌梗死/心肌梗死模型。再灌注28 d后,心肌梗死/心肌梗死大鼠分别给予CDT (300 mg/kg和600 mg/kg)、阿托伐他汀(2 mg/kg)和地尔硫卓(16 mg/kg)。超声心动图检查心脏功能和结构。采用免疫组化、马松三色染色、苏木精-伊红(HE)染色评价心肌组织纤维化及组织学改变。Western blotting检测自噬相关蛋白的表达。结果scdt能减轻心肌梗死/心肌梗死引起的心功能障碍、结构改变、组织病理改变及纤维化。CDT显著提高MI/RI大鼠Beclin1和微管相关蛋白1轻链3β (LC3β)水平,降低p62水平。此外,CDT显著增加单磷酸腺苷活化蛋白激酶(AMPK)的磷酸化,抑制哺乳动物雷帕霉素靶蛋白(mTOR)的磷酸化。结论cdt通过AMPK/mTOR信号通路激活自噬,提高自噬通量,改善心肌梗死/心肌梗死诱导的心室重构。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Chinese Herbal Medicines
Chinese Herbal Medicines CHEMISTRY, MEDICINAL-
CiteScore
4.40
自引率
5.30%
发文量
629
审稿时长
10 weeks
期刊介绍: Chinese Herbal Medicines is intended to disseminate the latest developments and research progress in traditional and herbal medical sciences to researchers, practitioners, academics and administrators worldwide in the field of traditional and herbal medicines. The journal's international coverage ensures that research and progress from all regions of the world are widely included. CHM is a core journal of Chinese science and technology. The journal entered into the ESCI database in 2017, and then was included in PMC, Scopus and other important international search systems. In 2019, CHM was successfully selected for the “China Science and Technology Journal Excellence Action Plan” project, which has markedly improved its international influence and industry popularity. CHM obtained the first impact factor of 3.8 in Journal Citation Reports (JCR) in 2023.
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