Department of Cardiovascular Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Maxillofacial Plastic Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
Drug Des Devel Ther. 2020 Sep 16;14:3765-3775. doi: 10.2147/DDDT.S239546. eCollection 2020.
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.
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.
Exosomes derived from mesenchymal stem cells could protect the myocardium against ischemia/reperfusion injury through inhibiting pyroptosis.
间充质干细胞（MSCs）在心肌细胞修复方面表现出独特的优势。MSC 来源的外泌体可以增强缺血/再灌注（I/R）损伤后心肌细胞的活力，并调节炎症反应。本研究旨在确定 MSC-exo 是否通过抑制细胞焦亡来保护心肌免受 I/R 损伤，以及潜在的机制。
在 H/R 和 I/R 模型中进行了实验。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 MSC-exo 处理 H/R 模型，流式细胞术分析结果显示 MSC-exo 对细胞凋亡具有抑制作用，Western blot 数据表明 H/R 模型中 NLRP3 和 Caspase-1 的表达下调。此外，外泌体 miR-320b 靶向 NLRP3 蛋白，MSC-exo OE 可抑制 H/R 中的 NLRP3 表达和细胞焦亡。此外，还在 I/R 模型中发现了 MSC-exo 对细胞焦亡的抑制作用，HE 和 Tunel 染色也得到了类似的结果。
MSC 来源的外泌体可以通过抑制细胞焦亡来保护心肌免受缺血/再灌注损伤。
