基于AF-Notch信号转导网络解析乳香-没药组分配伍促脑缺血后血管新生分子机制

Investigation of mechanisms and compatibility of components is one of difficulties in the research of TCMs. Frankincense-Myrrh compatibility dispels stasis, then promote regeneration. Many Chinese medicinal formulaes which are widely used for treatment of cerebrovascular diseases contain them. Our preliminary experiments indicate that AKBA and Z-GL reduce cerebral infarct volume and increase cerebral vessel intensity in ischemic area of MCAO rats. Moreover, they enhance tube formation and increase expression of VEGF and Notch1 in OGD treated HUEVCs. Therefore, the present study aims to demonstrate that AKBA and Z-GL modulate angiogenesis through intergration of multiple pathways. Firstly, differential gene expression profiles in ischemic cerebral tissues will be screened by using AF-Notch gene chips. Secondly, signal network will be built by analyzing differential genes with bioinformatics. Following, the pharmacological effects of AKBA and Z-GL on angiogenesis will be investigated by using cell biological technologies. The results will expand therapeutic strategy of Frankincense-Myrrh compatibility on cerebral ischemic injury. Taken together, the study will provide theoretical and experimental basis for various pathways that controlled by components of TCMs.

中药多成分多靶点的作用机制和配伍内涵是中药研究的难点。乳香-没药药对有“去瘀生新”之功效，以两者为核心的方剂在脑血管疾病应用广泛。我们前期研究证实，乳香中AKBA和没药中Z-GL显著减小缺血脑组织梗死面积，增加缺血区脑微血管密度，增强体外HUEVC细胞成管能力，并促进血管内皮生长因子VEGF和调控血管新生的细胞表面受体Notch1表达。本课题以AKBA和Z-GL为研究对象，构建血管生成因子和Notch信号转导通路（AF-Notch）基因芯片解析缺血脑组织的差异基因表达谱，结合生物信息学技术，建立信号调控网络，根据下游生物效应，采用细胞生物学技术研究药理作用机制，最终阐明乳香和没药有效组分AKBA和Z-GL通过多途径信号通路整合调节血管新生作用。研究结果不仅有望拓展乳香-没药防治脑缺血损伤的治疗思路，更为研究中药有效成分配伍的多途径调控规律提供理论和实验依据。

中药多成分多靶点的作用机制和配伍内涵是中药研究的难点。乳香-没药药对有“去瘀生新”之功效，以两者为核心的方剂在脑血管疾病应用广泛。本课题以AKBA和Z-GL为研究对象，解析缺血脑组织的差异基因表达谱，结合生物信息学技术，建立信号调控网络，根据下游生物效应，采用细胞生物学技术研究药理作用机制，最终阐明乳香和没药有效组分AKBA和Z-GL通过多途径信号通路发挥神经保护作用，并拓展研究临床常用中药制剂血塞通注射液的抗脑缺血损伤作用网络和核心调控通路。研究结果不仅有望拓展乳香-没药防治脑缺血损伤的治疗思路，更为研究中药有效成分配伍的多途径调控规律提供理论和实验依据。