Department of Geriatrics, Daqing Oilfield General Hospital, Daqing, Heilongjiang, P.R.China.
Bioengineered. 2022 Feb;13(2):3030-3043. doi: 10.1080/21655979.2021.2012402.
MicroRNA (miR)-150-5p has been investigated in many studies, while the role of exosomal miR-150-5p from bone arrow mesenchymal stromal cells (BMSCs) on cerebral ischemia/reperfusion (I/R) injury is not fully explored. This research aims to probe the effects of exosomal miR-150-5p from BMSCs on cerebral I/R injury via regulating B-cell translocation gene 2 (TLR5). Bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) were isolated and identified. The middle cerebral artery occlusion (MCAO) rat model was established and treated by BMSCs-Exo. Then, functional assays were conducted to explore neurological function, pathological changes, neuron apoptosis and inflammatory factors in MCAO rats. miR-150-5p and TLR5 expression in rat brain tissues were detected. Then, gain and loss-function assays were conducted to determine the impact of exosomes, miR-150-5p and TLR5 on neurological function, pathological changes, neuron apoptosis and inflammatory factors of MCAO rats. The binding relation between miR-150-5p and TLR5 was validated. It was found that miR-150-5p expression was decreased while TLR5 level was augmented in MCAO rats. BMSCs-Exo could improve neurological function, pathological changes, decelerate neuron apoptosis and reduce inflammatory factors in MCAO rats. Enriched miR-150-5pcould enhance the protective effects of BMSCs-Exo on cerebral I/R injury. The elevated TLR5 reversed the impacts of elevated exosomal miR-150-5p on cerebral I/R injury. TLR5 was targeted by miR-150-5p. This research manifested that exosomal miR-150-5p from BMSCs exerts protective effects on cerebral I/R injury via repressing TLR5. This study provided novel therapeutic targets for the treatment of cerebral I/R injury.
微小 RNA（miR）-150-5p 在许多研究中都有被研究过，然而骨髓间充质干细胞（BMSCs）来源的细胞外体 miR-150-5p 在脑缺血/再灌注（I/R）损伤中的作用尚未完全被探究。本研究旨在通过调节 B 细胞移位基因 2（TLR5）来探究 BMSCs 来源的细胞外体 miR-150-5p 对脑 I/R 损伤的影响。分离并鉴定骨髓间充质干细胞衍生的细胞外体（BMSCs-Exo）。建立大脑中动脉阻塞（MCAO）大鼠模型并通过 BMSCs-Exo 进行治疗。然后，进行功能测定以探究 MCAO 大鼠的神经功能、病理变化、神经元凋亡和炎症因子。检测大鼠脑组织中 miR-150-5p 和 TLR5 的表达。然后，进行增益和缺失功能测定以确定外体、miR-150-5p 和 TLR5 对 MCAO 大鼠神经功能、病理变化、神经元凋亡和炎症因子的影响。验证 miR-150-5p 与 TLR5 之间的结合关系。结果发现，MCAO 大鼠中 miR-150-5p 的表达降低而 TLR5 的水平升高。BMSCs-Exo 可改善 MCAO 大鼠的神经功能、病理变化、减缓神经元凋亡并减少炎症因子。富含 miR-150-5p 可增强 BMSCs-Exo 对脑 I/R 损伤的保护作用。升高的 TLR5 逆转了升高的外体 miR-150-5p 对脑 I/R 损伤的影响。TLR5 是 miR-150-5p 的靶标。本研究表明，BMSCs 来源的细胞外体 miR-150-5p 通过抑制 TLR5 对脑 I/R 损伤发挥保护作用。该研究为脑 I/R 损伤的治疗提供了新的治疗靶点。
