诸如神经生长因子（NGF）等药物因血脑屏障的阻挡难以入脑而丧失其治疗作用。星形胶质细胞在维持BBB的完整性方面发挥着重要作用，其分泌的Shh因子对 BBB结构和功能的影响备受关注。已有研究表明，Shh-Gli信号通路可以调控紧密连接转运蛋白，从而影响BBB通透性,同时电针对星形胶质细胞的活化具有调控作用。我们前期的研究发现，100Hz电针干预具有促血脑屏障开发效应，同时发现该开放效应具有一定的时间窗现象。本项目拟以100Hz电针经不同时长对脑缺血再灌注术后2周大鼠（脑缺血再灌注大鼠恢复期）进行干预，采用荧光定量、ELISA法观察伊文思蓝的透过效应；继而采用免疫荧光、Western Blotting、RT-PCR等技术探索电针如何通过Shh-Gli-TJ信号通路调控血脑屏障通透性的机制。本课题旨在研究电针辅助神经系统治疗药物进入血脑屏障并阐明其效应特征及可能机制。

Many nervous system drugs, such as NGF, cannot permeate through the brain and exert therapeutic effects due to the existence of the blood-brain barrier (BBB). Astrocytes play an important role in maintaining the integrity of BBB. Much attention has focused on the effect of astrocyte-derived Sonic hedgehog (Shh) on the structure and function of BBB. Evidence has suggested that Shh-Gli signaling pathway can affect the permeability of BBB by regulating tight junctional proteins. It is also known that electro-acupuncture (EA) can regulate the activation of astrocytes. Our previous studies have found that 100Hz EA intervention has opening effects on BBB. In addition, the opening effect of EA on BBB exhibited certain time window property. In this project, EA 100 Hz with different time duration is used to intervene at 2 weeks after cerebral ischemia-reperfusion injury in rats (the convalescence period of cerebral ischemia rat model). Fluorescent quantification and ELIAS will be used to study the permeation of Evans blue. Furthermore, immunofluorescent, Western blotting and RT-PCR, etc will be used to investigate the mechanisms of how EA regulates BBB permeability via Shh/Gli/TJ signaling pathway. The aim of this project is to characterize the effects of EA-aided permeation of nervous system drugs into the BBB and elucidate the underlying mechanisms.