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Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation.
Metabolic Brain Disease ( IF 3.6 ) Pub Date : 2020-03-17 , DOI: 10.1007/s11011-020-00563-w
Ibrahim Mohammed 1 , Sahar Ijaz 1 , Tahmineh Mokhtari 2, 3 , Morteza Gholaminejhad 1 , Marzieh Mahdavipour 1 , Behnamedin Jameie 4 , Mohammad Akbari 1 , Gholamreza Hassanzadeh 1
Affiliation  

Spinal cord injury (SCI) is the destruction of spinal cord motor and sensory resulted from an attack on the spinal cord, which can cause significant physiological damage. The inflammasome is a multiprotein oligomer resulting in inflammation; the NLRP3 inflammasome composed of NLRP3, apoptosis-associated speck-like protein (ASC), procaspase-1, and cleavage of procaspase-1 into caspase-1 initiates the inflammatory response. Subventricular Zone (SVZ) is the origin of neural stem/progenitor cells (NS/PCs) in the adult brain. Extracellular vesicles (EVs) are tiny lipid membrane bilayer vesicles secreted by different types of cells playing an important role in cell-cell communications. The aim of this study was to investigate the effect of intrathecal transplantation of EVs on the NLRP3 inflammasome formation in SCI rats. Male wistar rats were divided into three groups as following: laminectotomy group, SCI group, and EVs group. EVs was isolated from SVZ, and characterized by western blot and DLS, and then injected into the SCI rats. Real-time PCR and western blot were carried out for gene expression and protein level of NLRP3, ASC, and Caspase-1. H&E and cresyl violet staining were performed for histological analyses, as well as BBB test for motor function. The results indicated high level in mRNA and protein level in SCI group in comparison with laminectomy (p < 0.001), and injection of EVs showed a significant reduction in the mRNA and protein levels in EVs group compared to SCI (p < 0.001). H&E and cresyl violet staining showed recovery in neural cells of spinal cord tissue in EVs group in comparison with SCI group. BBB test showed the promotion of motor function in EVs group compared to SCI in 14 days (p < 0.05). We concluded that the injection of EVs could recover the motor function in rats with SCI and rescue the neural cells of spinal cord tissue by suppressing the formation of the NLRP3 inflammasome complex.

中文翻译:

脑室下区衍生的细胞外囊泡通过抑制 NLRP3 炎症小体复合物的形成促进脊髓损伤大鼠模型的功能恢复。

脊髓损伤(SCI)是由于脊髓受到攻击而引起的脊髓运动和感觉的破坏,可造成显着的生理损伤。炎性体是导致炎症的多蛋白寡聚体;由 NLRP3、凋亡相关斑点样蛋白 (ASC)、procaspase-1 和 procaspase-1 裂解为 caspase-1 组成的 NLRP3 炎性体启动炎症反应。脑室下区 (SVZ) 是成人大脑中神经干/祖细胞 (NS/PC) 的起源。细胞外囊泡 (EVs) 是由不同类型细胞分泌的微小脂膜双层囊泡,在细胞间通讯中起重要作用。本研究的目的是研究鞘内移植 EVs 对 SCI 大鼠 NLRP3 炎性体形成的影响。雄性wistar大鼠分为以下三组:椎板切除术组、SCI组和EVs组。从 SVZ 中分离出 EV,并通过蛋白质印迹和 DLS 进行表征,然后注射到 SCI 大鼠中。对 NLRP3、ASC 和 Caspase-1 的基因表达和蛋白质水平进行实时 PCR 和蛋白质印迹。H&E 和甲酚紫染色用于组织学分析,以及运动功能的 BBB 测试。结果表明,与椎板切除术相比,SCI 组的 mRNA 和蛋白质水平较高(p < 0.001),与 SCI 相比,EVs 的注射显示 EVs 组的 mRNA 和蛋白质水平显着降低(p < 0.001)。H&E 和甲酚紫染色显示与 SCI 组相比,EVs 组脊髓组织的神经细胞恢复。BBB 测试显示 EVs 组与 SCI 相比在 14 天内促进了运动功能(p < 0.05)。我们得出结论,注射 EVs 可以恢复 SCI 大鼠的运动功能,并通过抑制 NLRP3 炎症小体复合物的形成来挽救脊髓组织的神经细胞。
更新日期:2020-03-17
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