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Aloin Protects Against Blood-Brain Barrier Damage After Traumatic Brain Injury in Mice.
Neuroscience Bulletin ( IF 5.6 ) Pub Date : 2020-02-25 , DOI: 10.1007/s12264-020-00471-0
Yao Jing 1 , Dian-Xu Yang 1 , Wei Wang 1 , Fang Yuan 1 , Hao Chen 1 , Jun Ding 1 , Zhi Geng 2 , Heng-Li Tian 1
Affiliation  

Aloin is a small-molecule drug well known for its protective actions in various models of damage. Traumatic brain injury (TBI)-induced cerebral edema from secondary damage caused by disruption of the blood–brain barrier (BBB) often leads to an adverse prognosis. Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear, we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models. Adult male C57BL/6 mice underwent controlled cortical impact injury, and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury, then both received aloin treatment. In the animal experiments, we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema, decrease disruption of the BBB, and improve neurobehavioral performance after cortical impact injury. In the cellular studies, the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury. The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase, the activation of p65 nuclear factor-kappa B, and the ratios of B cell lymphoma (Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3. We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells. Aloin may thus be a promising therapeutic drug for TBI.

中文翻译:

Aloin可防止小鼠颅脑外伤后血脑屏障的损害。

Aloin是一种小分子药物,以其在各种损伤模型中的保护作用而闻名。外伤性脑损伤(TBI)引起的脑水肿是由血脑屏障(BBB)破坏引起的继发性损伤所致,通常会导致不良的预后。由于TBI后芦荟素在维持BBB完整性方面的作用尚不清楚,因此我们在体内体外探索了芦荟素对BBB的保护作用。TBI模型。成年雄性C57BL / 6小鼠受到可控的皮质撞击损伤,小鼠脑毛细血管内皮bEnd.3细胞受到双轴牵张损伤,然后均接受芦荟治疗。在动物实验中,我们发现20 mg / kg芦荟素是减少脑水肿,减少BBB破坏和改善皮质撞击损伤后神经行为表现的最佳浓度。在细胞研究中,最适浓度的40μg/ mL芦荟蛋白可通过降低活性氧水平和拉伸损伤后线粒体膜电位的变化来减少细胞凋亡并逆转紧密连接的丧失。其机制可能是芦荟蛋白下调了p38促分裂原激活蛋白激酶的磷酸化,p65核因子-κB的激活,B细胞淋巴瘤(Bcl)-2-相关X蛋白/ Bcl-2与裂解的caspase-3 / caspase-3的比率。我们得出的结论是,芦荟苷在TBI后通过其在小鼠脑毛细血管内皮细胞中的抗氧化应激和抗凋亡特性对BBB表现出这些保护作用。芦荟素因此可能是用于TBI的有前途的治疗药物。
更新日期:2020-02-25
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