Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Neurosci Bull. 2020 Jun;36(6):625-638. doi: 10.1007/s12264-020-00471-0. Epub 2020 Feb 25.
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.
芦荟素是一种小分子药物，因其在各种损伤模型中的保护作用而广为人知。创伤性脑损伤（TBI）引起的血脑屏障（BBB）破坏引起的继发性脑水肿，常导致不良预后。由于芦荟素在 TBI 后维持 BBB 完整性的作用尚不清楚，我们使用体内和体外 TBI 模型探讨了芦荟素对 BBB 的保护作用。成年雄性 C57BL/6 小鼠接受皮质撞击伤，小鼠脑微血管内皮细胞 bEnd.3 细胞接受双轴拉伸损伤，然后接受芦荟素治疗。在动物实验中，我们发现 20mg/kg 的芦荟素是降低脑水肿、减少 BBB 破坏和改善皮质撞击伤后神经行为表现的最佳浓度。在细胞研究中，最佳浓度的 40μg/mL 芦荟素可减少细胞凋亡，并通过降低拉伸损伤后活性氧水平和线粒体膜电位的变化来逆转紧密连接的丢失。其机制可能是芦荟素下调 p38 丝裂原活化蛋白激酶的磷酸化、p65 核因子-κB 的激活以及 B 细胞淋巴瘤（Bcl）-2 相关 X 蛋白/Bcl-2 和裂解 caspase-3/caspase-3 的比值。我们得出结论，芦荟素通过其在小鼠脑微血管内皮细胞中的抗氧化应激和抗细胞凋亡特性，对 TBI 后的 BBB 发挥这些保护作用。因此，芦荟素可能是一种有前途的 TBI 治疗药物。
