Sesamin alleviates blood-brain barrier disruption in mice with experimental traumatic brain injury
Sesamin alleviates blood-brain barrier disruption in mice with experimental traumatic brain injury
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芝麻素减轻实验性脑外伤小鼠的血脑屏障破坏
DOI：
10.1038/aps.2017.103
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发表时间：
2017-11-01
影响因子：
8.2
通讯作者：
Tian, Heng-li
中科院分区：
文献类型：
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作者：
Liu, Ying-liang;Xu, Zhi-ming;Tian, Heng-li
芝麻素是芝麻油中的一种主要木脂素，据报道在几种脑损伤模型中具有神经保护作用。然而，其在维持血脑屏障（BBB）完整性中的保护作用尚未被研究。在这项研究中，我们研究了芝麻素对创伤性脑损伤（TBI）小鼠血脑屏障的影响，并探讨了其潜在机制。将成年雄性C57BL/6小鼠进行控制性皮质冲击（CCI）损伤，然后给予芝麻素（30 mg·kg−1·d−1,ip）。分别于CCI损伤后第1天和第3天对小鼠实施安乐死，并采集标本进行分析。芝麻素处理在损伤后第1天和第3天显著减轻了cci所致的脑水肿，与载药组相比，同侧皮质组织含水量、组织血红蛋白水平、Evans蓝外渗和AQP4表达水平均有所降低。此外，芝麻素处理显著减轻了cci诱导的脑组织紧密连接蛋白ZO-1和occludin的丢失。进一步探讨芝麻素对培养小鼠脑微血管弯曲的神经保护机制。3个细胞遭受双向拉伸损伤（SI）。芝麻素预处理（50 μmol/L）可显著减轻si诱导的弯曲组织ZO-1的丢失。3细胞。此外，我们发现芝麻素预处理可显著减弱si诱导的bEnd氧化应激和早期凋亡。通过降低ERK、p-38和caspase-3的激活来抑制3细胞的凋亡。综上所述，芝麻素至少在一定程度上通过其对内皮细胞的抗氧化和抗凋亡作用减轻了血脑屏障的破坏。这些发现表明芝麻素可能是一种有希望的潜在治疗干预措施，可以预防脑外伤后血脑屏障的破坏。
Sesamin, a major lignan of sesame oil, was reported to have neuroprotective effects in several brain injury models. However, its protective action in maintaining blood-brain barrier (BBB) integrity has not been studied. In this study we investigated the effects of sesamin on the BBB in a mouse model of traumatic brain injury (TBI) and explored the underlying mechanisms. Adult male C57BL/6 mice were subjected to a controlled cortical impact (CCI) injury and then received sesamin (30 mg· kg− 1· d− 1, ip). The mice were euthanized on the 1 st and 3 rd days after CCI injury and samples were collected for analysis. Sesamin treatment significantly attenuated CCI-induced brain edema on the 1 st and 3 rd days after the injury, evidenced by the decreases in water content, tissue hemoglobin levels, Evans blue extravasation and AQP4 expression levels in the ipsilateral cortical tissue compared with the vehicle-treated group. Furthermore, sesamin treatment significantly alleviated CCI-induced loss of the tight junction proteins ZO-1 and occludin in the brain tissues. The neuroprotective mechanisms of sesamin were further explored in cultured mouse brain microvascular bEnd. 3 cells subjected to biaxial stretch injury (SI). Pretreatment with sesamin (50 μmol/L) significantly alleviated SI-induced loss of ZO-1 in bEnd. 3 cells. Furthermore, we revealed that pretreatment with sesamin significantly attenuated SI-induced oxidative stress and early-stage apoptosis in bEnd. 3 cells by decreasing the activation of ERK, p-38 and caspase-3. In conclusion, sesamin alleviates BBB disruption at least partly through its anti-oxidative and anti-apoptotic effects on endothelial cells in CCI injury. These findings suggest that sesamin may be a promising potential therapeutic intervention for preventing disruption of the BBB after TBI.