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

doi:https://doi.org/10.1016/j.chmed.2024.03.003

Archive > Volume 17 Issue 3 > 2025,17(3):548-554. DOI:https://doi.org/10.1016/j.chmed.2024.03.003 Prev Next

复方丹参片通过AMPK/mTOR信号通路调控自噬改善心肌缺血/再灌注损伤诱导的心室重构

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

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摘要:

目的：心肌缺血/再灌注损伤（MI/RI）导致的左心室重构是一种常见的心功能不全。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）对心室重构的改善作用及自噬是否为其潜在机制。方法：将大鼠左前降支暂时结扎30min，建立MI/RI模型。再灌注28 d诱导心室重构，在此期间给予MI/RI大鼠CDT（300 mg/kg和600 mg/kg）、阿托伐他汀（2 mg/kg）和地尔硫?（16 mg/kg）。超声心动检测大鼠心脏结构和功能。免疫组织化学、Masson三色染色和苏木精-伊红（H & E）染色用于评价心脏组织的纤维化和组织学改变。Western blot检测自噬相关蛋白的表达。结果：CDT减轻了MI/RI引起的心功能不全、结构改变、组织病理学改变和纤维化。CDT可显著提高MI/RI大鼠心脏Beclin1和微管相关蛋白1轻链3β（LC3β）的水平，降低p62的水平。此外，CDT显著增加腺苷酸活化蛋白激（AMPK）的磷酸化，并抑制哺乳动物雷帕霉素靶分子（mTOR）磷酸化。结论：CDT通过AMPK/mTOR信号通路激活自噬，改善自噬流，从而改善MI/RI诱导的心室重构。

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 (LC3b), 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.

关键词:

AMPK/mTOR信号通路;自噬;复方丹参片;心肌缺血/再灌注损伤;心室重构

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Project Supported:

This work was supported by Guangdong Province Key Field R&D Program Project (No. 2020B111111002) and the National Natural Science Foundation of China (No. U1812403-5-3; 81891012).

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复方丹参片通过AMPK/mTOR信号通路调控自噬改善心肌缺血/再灌注损伤诱导的心室重构

Original articles

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

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