艾灸督脉组穴调控周细胞PDGF-BB/PDGFRβ通路对VD大鼠血脑屏障的保护作用机制研究

VD是痴呆的第二大类型，中医病机为髓海不足，神机失用，而艾灸督脉具有益髓醒神之功，治疗VD疗效显著。研究认为BBB破坏是VD发病的关键环节，周细胞PDGF-BB/PDGFRβ信号通路在维持BBB稳定方面发挥重要作用。前期研究显示，艾灸督脉可通过调节VD大鼠脑微血管内皮分泌功能维持BBB稳定。由此我们假设：艾灸督脉可通过调节周细胞改善内皮细胞功能保护BBB。课题拟从PDGF-BB/PDGFRβ信号通路入手，观察艾灸督脉对VD大鼠周细胞覆盖率、BBB渗透率的影响，明确艾灸督脉对周细胞和BBB的保护作用；观察分泌环路Ang-1/Tie-2因子表达的变化，阐明艾灸督脉对周细胞及内皮细胞的调节机制；通过建立BBB缺氧损伤体外模型，调控周细胞PDGFRβ表达，验证周细胞PDGF-BB/PDGFRβ信号通路在VD模型BBB保护中的核心作用；为揭示艾灸督脉治疗VD的机制提供实验基础，并促进其临床应用。

VD is the second major kind of dementia. Deficiency of marrow sea and disuse of vital activity is VD’s etiology and pathogenesis of TCM. Based on the nourishing marrow and refreshing mind function of Moxibustion at Governor Meridian, it has significant effect on VD. Modern studies have found that BBB destruction is a common key link in the pathogenesis of VD, and pericyte PDGF-BB/PDGFRβ signaling pathway plays an important role in maintaining the stability of BBB. Previous research showed that Moxibustion of acupoints at Governor Meridian can maintain the stability of BBB via regulating the secretion function of endothelial cells in VD rats. Therefore, we propose the hypothesis that Moxibustion could improve the function of endothelial cells to protect BBB through regulating pericytes. Herein, we are going to focus mainly on the pericyte PDGF-BB/PDGFRβ signaling pathway. Firstly, the effects of Moxibustion on the pericyte’s coverage rate and BBB permeability of VD rats was observed, which clarify the protective effect of Moxibustion on pericytes and BBB. Secondly , the expression of Ang-1/Tie-2 paracrine loop factor were detected, which elucidate the regulatory mechanism of moxibustion on the pericytes and endothelial cells. Lastly, we will verify the key role of pericyte PDGF-BB/PDGFRβ signaling pathway in the protection of VD model BBB by establishing the BBB hypoxia injury model in vitro and regulating the expression of PDGFRβ in pericytes. So as to provide experimental basis for revealing the mechanism of Moxibustion at Governor Meridian in the treatment of VD and promote its clinical application.