Objective: Mesenchymal stem cells (MSCs) show unique advantages in cardiomyocyte repairment. Exosomes derived from MSCs can enhance the viability of myocardial cells after ischemia/reperfusion (I/R) injury and regulate inflammation response. The study was designed to ascertain whether MSCs-exo protect the myocardium against I/R injury through inhibiting pyroptosis, and the underlying mechanisms.
Methods and Results: Experiments were carried out in H/R and I/R model. Cell viability was inhibited and NLRP3 and caspase1 protein levels were upregulated in H/R model. However, MSCs could inhibit cell apoptosis and pyroptosis in H/R model. Moreover, we used MSCs-exo to treated H/R model, and flow cytometric analysis results showed the inhibition function of MSCs-exo on cell apoptosis, and Western blot data suggested that NLRP3 and Caspase-1 expressions were downregulated in H/R model. Furthermore, exosomal miR-320b targeted NLRP3 protein, and MSCs-exo OE could inhibit NLRP3 expression and pyroptosis in H/R. In addition, the inhibition function of MSCs-exo on pyroptosis also was found in I/R model, and HE and Tunel staining also got similar results.
Conclusion: Exosomes derived from mesenchymal stem cells could protect the myocardium against ischemia/reperfusion injury through inhibiting pyroptosis.

Keywords: exosome, mesenchymal stem cells, ischemia/reperfusion injury, pyroptosis, miR-320b


中文翻译：

---

间充质干细胞衍生的外泌体通过抑制细胞焦亡保护心肌免受缺血/再灌注损伤

目的：间充质干细胞（MSCs）在心肌细胞修复方面表现出独特的优势。来自 MSCs 的外泌体可以增强心肌细胞在缺血/再灌注 (I/R) 损伤后的活力并调节炎症反应。该研究旨在确定 MSCs-exo 是否通过抑制细胞焦亡保护心肌免受 I/R 损伤及其潜在机制。
方法和结果：实验在 H/R 和 I/R 模型中进行。在 H/R 模型中，细胞活力受到抑制，NLRP3 和 caspase1 蛋白水平上调。然而，MSCs可以抑制H/R模型中的细胞凋亡和细胞焦亡。此外，我们使用MSCs-exo处理H/R模型，流式细胞仪分析结果显示MSCs-exo对细胞凋亡的抑制作用，Western blot数据表明NLRP3和Caspase-1在H/R模型中表达下调。 . 此外，外泌体 miR-320b 靶向 NLRP3 蛋白，MSCs-exo OE 可以抑制 H/R 中 NLRP3 的表达和细胞焦亡。此外，MSCs-exo对细胞焦亡的抑制作用也在I/R模型中发现，HE和Tunel染色也得到了相似的结果。
结论：间充质干细胞来源的外泌体可通过抑制细胞焦亡来保护心肌免受缺血/再灌注损伤。

关键词：外泌体，间充质干细胞，缺血/再灌注损伤，细胞焦亡，miR-320b