厚朴酚对局灶性脑缺血/再灌注后血脑屏障损伤的保护效应及其机制研究

项目名称： 厚朴酚对局灶性脑缺血/再灌注后血脑屏障损伤的保护效应及其机制研究

项目编号： No.81503060

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘晓岩

作者单位： 北京大学

项目金额： 18.5万元

中文摘要： 脑卒中严重危害健康，脑缺血损伤时，血脑屏障（BBB）完整性破坏，加剧原发损伤并引起水肿和出血等继发性损伤，因此通过保护BBB治疗来减轻脑卒中损伤至关重要。厚朴酚是源自中药厚朴的小分子，其对脑卒中引起的神经损伤具有显著疗效。目前发现厚朴酚的脑保护机制包括抗炎、抗氧化和抗凋亡，其能否通过稳定BBB而起保护作用? BBB损伤与EphA2受体的激活密切相关，厚朴酚的作用是否与EphA2受体相关？仍然未知。本课题拟建立小鼠体外、体内BBB损伤模型，通过观察脑水肿、染料跨BBB渗出，以及BBB完整性相关蛋白表达变化，评价厚朴酚对BBB损伤的保护作用。并进一步通过激动剂和将EphA2受体转染到不表达细胞系中，观察厚朴酚处理后EphA2受体下游分子以及BBB的变化，以期发现EphA2受体在厚朴酚减轻BBB损伤中的作用。本研究将进一步阐明厚朴酚保护脑卒中的机制，为脑卒中的治疗提供新的理论依据。

中文关键词： 厚朴酚；脑缺血再灌注；血脑屏障；促红素人肝细胞受体A2

英文摘要： Stroke seriously harms to human health. when cerebral ischemic injury was happened, blood-brain barrier (BBB) integrity was damaged and thus brain edema and hemorrhage were exacerbated. Therefore, it is essential to reduce stroke damage by protecting BBB. Magnolol is a small molecule derived from traditional Chinese medicine Magnolia, which has a significant effect on protecting nerve damage caused by stroke. In previous studies, we have reported brain protection mechanisms of Magnolol included anti-inflammatory, antioxidant and anti-apoptotic. Can it play a protective role by stabilizing the BBB? Is there a close relationship between EphA2 receptor activation and BBB damage? Is the protective role of Magnolol related to the down regulation of EphA2 receptor? All of these are still unknown. The project is to evaluate the protective effect of Magnolol on BBB injury by observing cerebral edema, oozing dye cross BBB and BBB integrity-related protein expression changes through in vitro BBB damage model and in vivo I/R model. Furthermore, after EphA2 receptor activated or suppressed by the use of agonists or transfection of EphA2 receptor into b.End.3 cell line, the expression levels of EphA2、TJ、AJ、ZO-1 and MMP-9 related to EphA2 receptor and BBB structures in cells or tissues were determined after treated with Magnolol. After finish this project successfully, we hope to elucidate the molecular mechanisms of the interaction of Magnolol and EphA2 receptor during BBB injury. This research work will be helpful to provide a new theoretical basis for the treatment of stroke.

英文关键词： Magnolol;Cerebral ischemia reperfusion;The blood-brain barrier;EphA2