Electroacupuncture as a promising therapeutic strategy for doxorubicin-induced heart failure: Insights into the PI3K/AKT/mTOR/ULK1 and AMPK /mTOR /ULK1 pathways

IF 5.6 2区医学 Q1 BIOPHYSICS Colloids and Surfaces B: Biointerfaces Pub Date : 2025-02-26 DOI:10.1016/j.colsurfb.2025.114590

Peng Chao , Xueqin Zhang , Lei Zhang, Zhengyang Han, Runda Jie, Pingxiu Duan, Min Cao, Aiping Yang

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Abstract

Background

Electroacupuncture (EA), a traditional Chinese medicine therapy, exhibits cardioprotective and therapeutic effects against cardiac injury. However, the precise mechanisms underlying these benefits remain unclear.

Purpose

The aim of this study is to examine the impact of EA on Doxorubicin-Induced heart failure and elucidate the mechanisms involved.

Methods

C57BL/6 mice were randomly assigned to six experimental groups, including a control group, a DCM group, a DCM group receiving non-acupoint EA (NEA), and a DCM group receiving acupoint EA (EA). The cardiac function, levels of inflammatory factors, and markers of apoptosis were assessed both in vivo and in vitro. The presence of AMPK/mTOR/ULK1(Ser317) and PI3K/AKT/mTOR/ULK1(Ser757) was confirmed.

Results

EA stimulation significantly improved cardiac function, as evidenced by increased left ventricular ejection fraction (LVEF), E/A ratio, and fractional shortening (FS%) compared to the DCM group (p < 0.05). After EA stimulation, the phosphorylation levels of PI3K/AKT increase, leading to elevated expression of mTOR/ULK1(Ser757), which ultimately inhibited the expression of apoptosis-related proteins and inflammatory factors. Simultaneously, EA stimulation could inhibit the phosphorylation levels of AMPK, reducing the expression of mTOR/ULK1(Ser317), and thereby also inhibiting the expression of apoptosis-related proteins and inflammatory factors.

Conclusions

This study showed that EA stimulation can counteract myocardial damage caused by apoptosis and inflammation, thereby significantly improving cardiac function and prognosis in HF mice. The mechanism may be that EA stimulation activates the PI3K/AKT/mTOR/ULK1(ser757) pathway and inhibits the AMPK/ULK1(ser317) pathway. EA stimulation exerts the same effect by regulating these two pathways in different directions, ultimately reducing myocardial cell apoptosis and cardiac inflammation.

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电针作为阿霉素诱导心力衰竭的一种有前景的治疗策略：对PI3K/AKT/mTOR/ULK1和AMPK /mTOR/ULK1通路的见解

背景：电针作为一种传统的中医疗法，对心脏损伤具有保护和治疗作用。然而，这些益处背后的确切机制尚不清楚。目的探讨EA对阿霉素诱导心力衰竭的影响，并探讨其作用机制。方法将sc57bl /6小鼠随机分为6个实验组，分别为对照组、DCM组、DCM组（非穴位EA）和DCM组（穴位EA）。在体内和体外评估心脏功能、炎症因子水平和细胞凋亡标志物。证实了AMPK/mTOR/ULK1（Ser317）和PI3K/AKT/mTOR/ULK1（Ser757）的存在。结果与DCM组相比，sea刺激可显著改善心功能，左室射血分数（LVEF）、E/A比和缩短分数（FS%）均显著增加（p <； 0.05）。EA刺激后，PI3K/AKT磷酸化水平升高，导致mTOR/ULK1（Ser757）表达升高，最终抑制凋亡相关蛋白和炎症因子的表达。同时，EA刺激可以抑制AMPK的磷酸化水平，降低mTOR/ULK1（Ser317）的表达，从而抑制凋亡相关蛋白和炎症因子的表达。结论EA刺激可抵消心肌细胞凋亡和炎症引起的心肌损伤，显著改善心功能和预后。其机制可能是EA刺激激活PI3K/AKT/mTOR/ULK1（ser757）通路，抑制AMPK/ULK1（ser317）通路。EA刺激通过不同方向调节这两种通路发挥相同的作用，最终减少心肌细胞凋亡和心脏炎症。

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

Colloids and Surfaces B: Biointerfaces 生物-材料科学：生物材料

CiteScore

11.10

自引率

3.40%

发文量

730

审稿时长

42 days

期刊介绍： Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.