To explore the therapeutic effect and possible mechanism of exosomes from MSCs overexpressing miR-223 on cerebral ischemia and microglia polarization mediated inflammation. Rats after middle cerebral artery occlusion and reperfusion (MCAO/R) surgery and microglia BV-2 exposed to oxygen and glucose deprivation (OGD) and cysteinyl leukotrienes (CysLTs) stimulation were subject to exosomes from miR-223-3p transfected MSCs treatment, respectively. Behavioral tests were applied to assess the rats' neurological function. FACS was used to analyze M1/M2 microglia BV-2. production of cytokines in the ischemic hemisphere and BV-2 was detected by ELISA or qRT-PCR. Western blotting and qRT-PCR were also used to examine the expression of cysteinyl leukotriene receptor 2 (CysLTR) and . Exosomes from MSCs over expressing miR-223-3p decreased MCAO/R induced cerebral infarct volume, improved neurological deficits, promoted learning and memorizing abilities. They suppressed pro-inflammatory factors expression and promoted anti-inflammatory factors secretion in the ischemic cortex and hippocampus. , exosomal miR-223-3p exhibited a more evident impact on modulating mRNA expression and protein production of cytokines. It promoted M2 microglia transformation of M1 microglia induced by NMLTC with a concentration-dependent manner. Western blot and qRT-PCR also revealed exosomal miR-223-3p decreased mRNA and protein expression of CysLTR and . Exosomal miR-223-3p from MSCs attenuated cerebral ischemia/reperfusion injury through inhibiting microglial M1 polarization mediated pro-inflammatory response, which may be related with inhibitory effect of exosomal miR-223-3p on CysLTR.

中文翻译：

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来自过表达 microRNA-223-3p 的 MSC 的外泌体通过抑制小胶质细胞 M1 极化介导的炎症来减轻脑缺血


探讨过表达miR-223的间充质干细胞外泌体对脑缺血和小胶质细胞极化介导的炎症的治疗作用及可能机制。大脑中动脉闭塞和再灌注 (MCAO/R) 手术后的大鼠以及暴露于氧糖剥夺 (OGD) 和半胱氨酰白三烯 (CysLTs) 刺激的小胶质细胞 BV-2 分别接受来自 miR-223-3p 转染的 MSC 的外泌体治疗。应用行为测试来评估大鼠的神经功能。 FACS 用于分析 M1/M2 小胶质细胞 BV-2。通过ELISA或qRT-PCR检测缺血半球和BV-2中细胞因子的产生。还使用蛋白质印迹和 qRT-PCR 检测半胱氨酰白三烯受体 2 (CysLTR) 和 的表达。来自过度表达 miR-223-3p 的 MSC 的外泌体可减少 MCAO/R 诱导的脑梗塞体积，改善神经功能缺损，促进学习和记忆能力。它们抑制缺血皮质和海马中促炎因子的表达并促进抗炎因子的分泌。 ，外泌体miR-223-3p对调节细胞因子的mRNA表达和蛋白质产生表现出更明显的影响。它以浓度依赖性方式促进 NMLTC 诱导的 M1 小胶质细胞向 M2 小胶质细胞转化。 Western blot 和 qRT-PCR 还显示，外泌体 miR-223-3p 降低了 CysLTR 和 的 mRNA 和蛋白表达。间充质干细胞外泌体miR-223-3p通过抑制小胶质细胞M1极化介导的促炎症反应减轻脑缺血/再灌注损伤，这可能与外泌体miR-223-3p对CysLTR的抑制作用有关。