三七丹参有效组分配伍促进脑中风恢复的脑神经血管单元整合机制研究

缺血性脑中风除急性期溶栓治疗外，国外脑保护剂研发迄未成功。中药临床恢复其应用广泛且疗效显著，但如何发挥多成分协同作用促进脑功能恢复及机制研究有待深入。本研究根据中医学理论在中风恢复期益气活血治则为主指导下，以益气活血代表药三七和丹参注射制剂注射用血栓通和丹参多酚酸有效成分为研究对象，在前期工作基础上，重点从促进恢复期神经血管单元整合修复机制方面，研究两种制剂有效成分对中风后血管神经单元各组成及相互作用的影响。体外采用脑微血管内皮细胞、星形胶质细胞、小胶质细胞培养及微血管内皮细胞/星形胶质细胞/周细胞共培养血脑屏障（BBB）模型，以及大脑中动脉栓塞脑缺血大鼠模型，选择注射用血栓通和丹参多酚酸有效成分，从BBB透过性、保护BBB结构与功能、基底膜细胞外基质重建相关因子表达的影响，以及促进神经元再生、血管新生、突触修复、动物神经功能恢复等方面，探讨中药多成分协同作用。

Except to thrombolytic treatment in acute phase of ischemic stroke, all neuroprotection agents R&D failed by far in abroad. Although Traditional Chinese medicine have been Widely used in clinic and proved effective, mechanism of multi-component synergies and how they promote brain function recovery still need further study. In present study, according to the treatment method of nourashing Qi and promote blood circulation in TCM theory during chronic phase of post-stroke, effective constituents in Xueshuantong Injection and Danshenduofensuan Injection are selected as representative active component constituents of Panax notoginsen and Danshen, the neurovascular remodeling mechanism of the promotive action by combination use of constituents derived from Pannax notoginsen and Danshen during post-stroke recovery are to be elucidated. Based on the previous preliminary experimental results, both in vitro and in vivo study are included. Primary culture of brain microvascular endothelial cells(BMEC), astrocytes(AS), microglia and BMEC/AS/pericyte coculture blood-brain barrier (BBB) model will be established, MCAo rodent model are to be used. BBB permeability, protection for BBB structure and function, impact on the basement membrane, remodeling of extracellular matrix(ECM) are to be studied. As well, promotion effects to neurogenesis, angiogegesis, synaptic repair, neurologic function recovery of the single and combination use of the active component constituents of Panax notoginsen and Danshen in two injections are to be studied. The aim of the study is to explore multi-component synergic action mechanism of the active constituents of active components of Panax notoginsen and Danshen and their compitibility related to neurovascular remodeling, provide more scientific evidence of the combination use of multi-constituents derived from Traditional Chinese medicine for promoting post-stroke recovery, illustrate the advantages of traditional Chinese medicine’s neuroprotection effects and guide the applications of traditional Chinese medicine in clinic.