Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimen, Beijing 100700, China.
CNS Neurol Disord Drug Targets. 2013 Sep;12(6):882-93. doi: 10.2174/18715273113129990073.
Until now the overlapping and diverse pharmacological protective mechanisms of different compounds in the treatment of cerebral ischemia, both on the signaling pathway and network levels have not been revealed. In order to find differential pathway networks from gene expression profiles of hippocampus of ischemic mice treated with baicalin (BA), ursodeoxycholic acid (UA) and jasminoidin (JA), a microarray comprising 16,463 genes, FDA Arraytrack software and Ingenuity Pathway Analysis, was employed. A total of 5, 8, 11, 9 networks and 6, 7, 40, 16 pathways were found in vehicle (vs sham), BA, UA and JA (vs vehicle), respectively. Only 4 and 7 overlapping pathways were shared between BA and UA, UA and JA, accounting for 9.3% and 14.3% of the total number of all pathways, respectively. BA, UA and JA all acted on Ca(2+)-dependent signaling cascades in diverse links. BA intervened in arachidonic acid metabolism. UA affected eicosanoid, cyclin-dependent kinase 5, nuclear factor-kB, and T-helper 1 cell cytokine production. It was found that JA might decrease oxidative damage via nuclear factor erythroid 2-related factor 2-mediated antioxidant response. Compared to vehicle, no overlapping pathways were found among three groups. However, the total of 60 (71.4%) overlapping functions could be approximately divided into diseases and disorders, molecular and cellular functions, physiological system development and function as categories with ratio of 1:1:1. Analysis of network functions and known pathways may be two complementary paradigms for revealing potential pharmacological mechanisms based on the same phenotype variation.
到目前为止，尚未揭示不同化合物在治疗脑缺血方面的重叠和多样化的药理学保护机制，无论是在信号通路还是网络水平上。为了从黄芩素（BA）、熊去氧胆酸（UA）和茉莉酸（JA）处理缺血性小鼠海马的基因表达谱中找到差异途径网络，采用了包含 16463 个基因的微阵列、FDA Arraytrack 软件和 Ingenuity 通路分析。在载体（与假手术相比）、BA、UA 和 JA（与载体相比）中分别发现了 5、8、11、9 个网络和 6、7、40、16 条途径。BA 和 UA、UA 和 JA 之间仅共享 4 和 7 个重叠途径，分别占所有途径总数的 9.3%和 14.3%。BA、UA 和 JA 均作用于不同环节的 Ca(2+)-依赖性信号级联。BA 干预花生四烯酸代谢。UA 影响前列腺素、周期蛋白依赖性激酶 5、核因子-kB 和 T 辅助 1 细胞细胞因子的产生。发现 JA 可能通过核因子红细胞 2 相关因子 2 介导的抗氧化反应来降低氧化损伤。与载体相比，三组之间没有重叠途径。然而，在三组中总共发现了 60 个（71.4%）重叠功能，这些功能可以大致分为疾病和紊乱、分子和细胞功能、生理系统发育和功能三大类，比例为 1:1:1。网络功能和已知途径的分析可能是基于相同表型变化揭示潜在药理学机制的两种互补范例。
