Shenxiong Yixin Decoction polysaccharides exert therapeutic effects against myocardial ischemia-reperfusion injury via intestinal exosomal microRNA-21 regulation

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research Pub Date : 2025-04-08 DOI:10.1016/j.phrs.2025.107725

De-Sheng Xu , Yan Wang , Zi-Rui Li , Ping-Li Mo , Ming-Tai Chen , Rui-Zhi Zhao , Zheng Fan , Wen-Jie Mo , Qi-Lu Li , Fang-Cao Pi , Qi-Di Sun , Juan-Min Li , Yun-Da Yao , Jian-Ping Chen , Yuan-Yuan Li , Jie-Nan Luan , Shang-Bin Zhang , Ying Xie , Hua Zhou

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引用次数: 0

Abstract

Background and Objective: Myocardial ischemia-reperfusion injury (MIRI) presents a prevalent global clinical challenge without an optimal treatment strategy. Shenxiong Yixin Decoction exhibits promising cardioprotective effects in clinical scenarios. Polysaccharides, particularly pivotal in cardioprotection, act systemically through the intestine. Exosomes, particularly miRNA-rich ones, are crucial in MIRI pathophysiology. However, the specific role of gut-derived exosomal miRNAs in cardiovascular disease remains unclear. This study aimed to evaluate the cardioprotective effects of Shenxiong Yixin Decoction polysaccharides (SXYXP) on MIRI and elucidate its mechanisms.

Methods

In vitro and in vivo models of MIRI were set up with H9c2 cells, C57BL/6 mice, and Sprague-Dawley rats. Exosomes from IEC-6 cells and plasma were detected. Various techniques like MTT, TTC, H&E staining, echocardiography, flow cytometry, immunofluorescence, RT-qPCR, and Western blot were employed for pharmacodynamic and mechanistic analyses.

Results

SXYXP treatment could reduce myocardial infarction area, improve cardiac function, and increase myocardial cell survival rate under MIRI. The SXYXP treatment significantly enhanced the release of enterocyte-derived exosomes and elevated the levels of miR-21 within these exosomes. These SXYXP-modulated exosomes demonstrated a significant protective effect against H/R injury in H9c2 cells. However, the application of miR-21 inhibitors in the SXYXP group negated the protective effects of exosomes, leading to diminished cardiomyocyte proliferation, exacerbated oxidative stress, and elevated apoptosis.

Conclusion

SXYXP may protect against MIRI by targeting miR-21 in intestinal cell-derived exosomes, which are transported to the heart through the blood to restore the level of miR-21 in the damaged myocardium, thereby inhibiting oxidative stress and the expression of PDCD4.

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参熊益心汤多糖通过调节肠外泌体microRNA-21对心肌缺血再灌注损伤的作用

背景和目的：心肌缺血再灌注损伤（MIRI）是一个普遍存在的全球性临床难题，目前尚无最佳治疗策略。神芎养心煎剂在临床中显示出良好的心脏保护作用。多糖在心脏保护中尤为关键，可通过肠道在全身发挥作用。外泌体，尤其是富含 miRNA 的外泌体，在 MIRI 病理生理学中至关重要。然而，肠道外泌体 miRNA 在心血管疾病中的具体作用仍不清楚。本研究旨在评估神芎益心煎多糖（SXYXP）对 MIRI 的心脏保护作用，并阐明其机制。检测了 IEC-6 细胞和血浆中的外泌体。采用 MTT、TTC、H&E 染色、超声心动图、流式细胞术、免疫荧光、RT-qPCR 和 Western 印迹等多种技术进行药效学和机理分析。SXYXP 治疗可明显促进肠细胞衍生外泌体的释放，并提高这些外泌体中 miR-21 的水平。这些经 SXYXP 调控的外泌体对 H9c2 细胞的 H/R 损伤具有明显的保护作用。结论 SXYXP 可通过靶向肠细胞衍生外泌体中的 miR-21，使其恢复受损心肌中的 miR-21 水平，从而抑制氧化应激和 PDCD4 的表达，从而抵御 MIRI。

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

Pharmacological research 医学-药学

CiteScore

18.70

自引率

3.20%

发文量

491

审稿时长

8 days

期刊介绍： Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.