Department of Operation Room, Heart Center, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Curr Neurovasc Res. 2020;17(2):155-163. doi: 10.2174/1567202617666200214103950.
The effects of mesenchymal stem cell (MSC)-derived exosomes on brain microvascular endothelial cells under oxygen-glucose deprivation (OGD), which mimic cells in deep hypothermic circulatory arrest (DHCA) in vitro, are yet to be studied.
MSCs were co-cultured with primary rat brain endothelial cells, which were then exposed to OGD. Cell viability, apoptosis, the inflammatory factors (IL-1β, IL-6, and TNF-α), and the activation of inflammation-associated TLR4-mediated pyroptosis and the NF-κB signaling pathway were determined. Furthermore, exosomes derived from MSCs were isolated and incubated with endothelial cells to investigate whether the effect of MSCs is associated with MSCderived exosomes. Apoptosis, cell viability, and the inflammatory response were also analyzed in OGD-induced endothelial cells incubated with MSC-derived exosomes.
OGD treatment promoted endothelial cell apoptosis, induced the release of inflammatory factors IL-1β, IL-6, and TNF-α, and inhibited cell viability. Western blot analysis showed that OGD treatment-induced TLR4, and NF-κB p65 subunit phosphorylation and caspase-1 upregulation, while co-culture with MSCs could reduce the effect of OGD treatment on endothelial cells. As expected, the effect of MSC-derived exosomes on OGD-treated endothelial cells was similar to that of MSCs. MSC-derived exosomes alleviated the OGD-induced decrease in the viability of endothelial cells, and increased levels of apoptosis, inflammatory factors, and the activation of inflammatory and inflammatory focal pathways.
Both MSCs and MSC-derived exosomes attenuated OGD-induced rat primary brain endothelial cell injury. These findings suggest that MSC-derived exosomes mediate at least some of the protective effects of MSCs on endothelial cells.
研究间充质干细胞（MSC）衍生的外泌体对体外深低温停循环（DHCA）中细胞模拟的氧葡萄糖剥夺（OGD）下脑微血管内皮细胞的影响。
将 MSC 与原代大鼠脑内皮细胞共培养，然后使其暴露于 OGD。测定细胞活力、凋亡、炎症因子（IL-1β、IL-6 和 TNF-α）以及与炎症相关的 TLR4 介导的细胞焦亡和 NF-κB 信号通路的激活。此外，分离 MSC 衍生的外泌体并孵育内皮细胞，以研究 MSC 的作用是否与 MSC 衍生的外泌体有关。还分析了在 OGD 诱导的内皮细胞中孵育 MSC 衍生的外泌体后细胞凋亡、细胞活力和炎症反应。
OGD 处理促进内皮细胞凋亡，诱导炎症因子 IL-1β、IL-6 和 TNF-α的释放，并抑制细胞活力。Western blot 分析显示，OGD 处理诱导 TLR4 和 NF-κB p65 亚基磷酸化以及 caspase-1 的上调，而与 MSC 共培养可减轻 OGD 处理对内皮细胞的影响。正如预期的那样，MSC 衍生的外泌体对 OGD 处理的内皮细胞的作用与 MSC 相似。MSC 衍生的外泌体减轻了 OGD 诱导的内皮细胞活力下降，并增加了细胞凋亡、炎症因子以及炎症和炎症焦点途径的激活水平。
MSC 和 MSC 衍生的外泌体均减轻了 OGD 诱导的大鼠原代脑内皮细胞损伤。这些发现表明，MSC 衍生的外泌体至少介导了 MSC 对内皮细胞的部分保护作用。
