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生物活性(RS)-萝卜硫苷对实验性自身免疫性脑脊髓炎后小鼠血脑屏障通透性的保护作用。

The protective effects of bioactive (RS)-glucoraphanin on the permeability of the mice blood-brain barrier following experimental autoimmune encephalomyelitis.

作者信息

Giacoppo S, Galuppo M, Iori R, De Nicola G R, Bramanti P, Mazzon E

机构信息

IRCCS Centro Neurolesi "Bonino-Pulejo", Contrada Casazza, Messina, Italy.

出版信息

Eur Rev Med Pharmacol Sci. 2014;18(2):194-204.

Abstract

OBJECTIVES

Alterations in blood-brain barrier (BBB) permeability are due to the disruption of the Tight Junctions (TJs), large multiprotein complexes important for the maintenance of structural integrity and for permeability of the barrier. In this experimental study we evaluated the neuroprotective role of (RS)-glucoraphanin, a glucosinolate present in Brassicaceae, notably in Tuscan black kale, and bioactivated with myrosinase enzyme (bioactive RS-GRA) (10 mg/kg/d intraperitoneally), to prevent the dysfunction of BBB, in an experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS).

MATERIALS AND METHODS

EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55 in mice. By western blot analysis of brain tissues, we evaluated expression and distribution of the TJ-associated proteins, claudin-1, -3, -5 and ZO-1. Additionally, in order to gain a better insight into the mechanisms of action of bioactive RS-GRA, we investigated Foxp3, ERK1/2 and caspase 3 expression associated both to inflammatory response as well as to apoptotic pathway.

RESULTS

Our results demonstrated that treatment with bioactive RS-GRA counteracts the alteration of all these parameters and preserves TJ integrity through an antinflammatory and antiapoptotic activity during MS.

CONCLUSIONS

Bioactive RS-GRA, could be a therapeutic perspective helpful in preventing dysfunction of the BBB.

摘要

目的

血脑屏障(BBB)通透性的改变是由于紧密连接(TJ)的破坏,紧密连接是一种大型多蛋白复合物,对维持结构完整性和屏障通透性至关重要。在本实验研究中,我们评估了(RS)-萝卜硫素的神经保护作用,萝卜硫素是十字花科植物中存在的一种硫代葡萄糖苷,特别是在托斯卡纳黑甘蓝中,并经黑芥子酶生物活化(生物活性RS-GRA)(10mg/kg/d腹腔注射),以预防实验性自身免疫性脑脊髓炎(EAE)(一种多发性硬化症(MS)模型)中血脑屏障的功能障碍。

材料和方法

通过用髓鞘少突胶质细胞糖蛋白肽(MOG)35-55免疫小鼠诱导EAE。通过对脑组织进行蛋白质印迹分析,我们评估了TJ相关蛋白claudin-1、-3、-5和ZO-1的表达和分布。此外,为了更好地了解生物活性RS-GRA的作用机制,我们研究了与炎症反应以及凋亡途径相关的Foxp3、ERK1/2和caspase 3的表达。

结果

我们的结果表明,生物活性RS-GRA治疗可抵消所有这些参数的改变,并在MS期间通过抗炎和抗凋亡活性维持TJ完整性。

结论

生物活性RS-GRA可能是预防血脑屏障功能障碍的一种有帮助的治疗方法。

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