Wu Chuanhong, Chen Jianxin, Chen Chang, Wang Wei, Wen Limei, Gao Kuo, Chen Xiuping, Xiong Sihuai, Zhao Huihui, Li Shaojing
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China.
Sci Rep. 2015 Nov 5;5:16151. doi: 10.1038/srep16151.
Microenvironmental regulation has become a promising strategy for complex disease treatment. The neurovascular unit (NVU), as the key structural basis to maintain an optimal brain microenvironment, has emerged as a new paradigm to understand the pathology of stroke. In this study, we investigated the effects of galangin, a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, on NVU microenvironment improvement and associated signal pathways in rats impaired by middle cerebral artery occlusion (MCAO). Galangin ameliorated neurological scores, cerebral infarct volume and cerebral edema and reduced the concentration of Evans blue (EB) in brain tissue. NVU ultrastructural changes were also improved by galangin. RT-PCR and western blot revealed that galangin protected NVUs through the Wnt/β-catenin pathway coupled with HIF-1α and vascular endothelial growth factor (VEGF). VEGF and β-catenin could be the key nodes of these two coupled pathways. In conclusion, Galangin might function as an anti-ischemic stroke drug by improving the microenvironment of NVUs.
微环境调节已成为治疗复杂疾病的一种有前景的策略。神经血管单元（NVU）作为维持最佳脑微环境的关键结构基础，已成为理解中风病理学的新范例。在本研究中，我们研究了从高良姜根茎中分离出的天然黄酮类化合物高良姜素对大脑中动脉闭塞（MCAO）损伤大鼠的NVU微环境改善及相关信号通路的影响。高良姜素改善了神经功能评分、脑梗死体积和脑水肿，并降低了脑组织中伊文思蓝（EB）的浓度。高良姜素还改善了NVU的超微结构变化。逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法（western blot）显示，高良姜素通过与缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）耦合的Wnt/β-连环蛋白途径保护NVU。VEGF和β-连环蛋白可能是这两条耦合途径的关键节点。总之，高良姜素可能通过改善NVU的微环境发挥抗缺血性中风药物的作用。
