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

作者：XU De-sheng, Yan Wang, Zirui Li, Pingli Mo, Mingtai Chen, Ruizhi Zhao, Zheng Fan, Wenjie Mo, Q Y Li, F Pi, Qidi Sun, J Li, Yun-Da Yao, Jianping Chen, Yuanyuan Li, Jienan Luan, Shang-Bing Zhang, Ying Xie, Hua Zhou · 发表于：Pharmacological Research · 年份：2025 · DOI：10.1016/j.phrs.2025.107725 · 被引用次数：16 · 研究领域：Extracellular vesicles in disease、Transplantation: Methods and Outcomes、Cardiac Ischemia and Reperfusion

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 negat...