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首页> 外文期刊>Life sciences >Beneficial effects of (RS)-glucoraphanin on the tight junction dysfunction in a mouse model of restraint stress
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Beneficial effects of (RS)-glucoraphanin on the tight junction dysfunction in a mouse model of restraint stress

机译：（RS）-葡萄糖尿素对束缚应激小鼠模型中紧密连接功能障碍的有益作用

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Aims The purpose of this work is to evaluate the effects of (R S)-glucoraphanin, a glucosinolate present in Brassicaceae, notably in Tuscan black kale, and bioactivated with myrosinase enzyme (bioactive R S-GRA) (10 mg/kg intraperitoneally), and to assess its capacity to prevent the dysfunction of the blood-brain barrier (BBB), a fundamental structure for brain homeostasis, in a mouse model of restraint stress. Main methods CD1 mice were subjected to restraint stress by blocking the body with a tape on a table for 150 min at the four extremities. After the sacrifice of the animals, stomachs and brains were collected to perform histological evaluation, Evan's blue dye, immunohistochemistry and western blotting analysis, to evaluate whether immobilization stress leads to alterations of tight junction (TJ) components, such as claudin-1, claudin-3 and ZO-1. Key findings Immobilization causes considerable damage to BBB as shown by detection of Evan's blue dye, indicating a high level of extravasation due to stress. BBB alterations were accompanied by an enhancement of GFAP expression, IkB-alpha degradation followed by increased NF-kBp65 nuclear translocation, as well as caspase 3 overexpression. Conversely, our results revealed that bioactive R S-GRA treatment significantly counteracts the changes in all these parameters and preserves TJ integrity reducing the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, and increasing the production of IL-10, an anti-inflammatory cytokine. Additionally, bioactive RS-GRA shows antioxidant properties modulating iNOS and nitrotyrosine expression. Significance Our results clearly show that bioactive R S-GRA could represent a possible treatment during pharmacological therapy of stress.
机译：目的这项工作的目的是评估（RS）-葡萄糖苷，一种存在于十字花科，特别是托斯卡纳黑羽衣甘蓝中的芥子油苷，并通过黑芥子酶（生物活性R S-GRA）（腹膜内10 mg / kg）进行生物活化，并在抑制应激的小鼠模型中评估其预防血脑屏障（BBB）功能失调的能力，血脑屏障是大脑动态平衡的基本结构。主要方法CD1小鼠在桌子上的四个肢体上用胶带粘住身体150分钟，从而受到约束压力。处死动物后，收集胃和大脑进行组织学评估，Evan的蓝色染料，免疫组织化学和蛋白质印迹分析，以评估固定化应激是否导致紧密连接（TJ）组件（例如claudin-1，claudin）发生改变。 -3和ZO-1。主要发现固定化会对BBB造成相当大的损害，如检测到Evan的蓝色染料所表明的那样，表明由于压力而大量外渗。 BBB改变伴随着GFAP表达增强，IkB-alpha降解继之以NF-kBp65核易位增加以及caspase 3过表达。相反，我们的结果表明，生物活性R S-GRA治疗可显着抵消所有这些参数的变化，并保留TJ完整性，从而减少促炎性细胞因子（如TNF-α和IL-1β）的产生，并增加IL- 10，抗炎细胞因子。此外，具有生物活性的RS-GRA具有抗氧化特性，可调节iNOS和硝基酪氨酸的表达。意义我们的结果清楚地表明，生物活性R S-GRA可能代表药物在应激药物治疗期间的可能治疗方法。

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