活血潜阳颗粒对自发性高血压大鼠大脑组织基因表达谱的影响

Influence of Huoxueqianyang granule on spontaneously hypertension rats cerebral gene expression profiles

目的采用基因芯片技术研究活血潜阳颗粒对自发性高血压大鼠(SHR)脑组织基因表达谱的影响,探讨该药保护高血压靶器官的分子机制。方法12只20周龄雄性SHR随机分为干预组(活血潜阳颗粒组)和对照组;从脑组织中抽提mRNA,经逆转录分别用Cy3、Cy5荧光标记,获得2组动物来源的cDNA探针;cDNA探针与基因表达谱芯片杂交,结果由扫描仪扫描并用软件进行分析统计。结果SHR给予活血潜阳颗粒药物干预8周后,收缩压明显下降。全基因表达谱差异表达基因共有1290个,下调的基因有611个,361个能在Genbank上登陆;上调的基因679个,360个基因能在Genbank上登陆。其中活血潜阳颗粒组SHR脑组织中Wif-1、Ppp2ca、EPO、Crk、Daxx、PPARδ等存在显著基因差异表达。这些表达差异基因涉及Wnt、JAK-STAT、MAPK、PPAR等多个信号传导通路。结论活血潜阳颗粒可能通过Wnt、JAK-STAT、MAPK、PPAR等信号传导通路相关基因的干预从而对高血压慢性脑损害起一定防治作用。

Objective To observe the influence of Huoxueqianyang granule on spontaneously hypertensive rats（SHR） cerebral gene expression profiles by using gene chip technique,research the possible molecular mechanism of Huoxueqianyang granules in protecting target organs of hypertension.Methods 12 male SHR at 20 weeks were divided into 2 groups randomly with 6 in each group：interference group（Huoxueqianyang granule group） and control group.The total mRNA was extracted from the brain of SHR,the total RNA was reverse transcribed to cDNA marked by Cy3 and Cy5 in vitro,then cDNA was hybridized with gene expression profile chip,and gene expression was analyzed using Agilent microarray technology.The functions of the differentially expressed genes were analyzed by bioinformatics.Results Compared with control group,systolic blood pressures of SHR in interference group decreased obviously after 8 weeks treatment.Totally there were 1290 genes changed between interference group and control group,611 genes were regulated downward of which 361 genes could login the Genbank,679 genes were regulated upward of which 360 genes could login Genbank.Several genes including Wif-1,Ppp2ca,EPO,Crk,Daxx,PPARδexpressed differentially in Huoxueqianyang granule group,which influenced Wnt,JAK-STAT,MAPK,PPAR,etc,cell signaling transduction pathways.Conclusion Huoxueqianyang granule play an important role in the prevention and treatment of hypertensive chronic cerebral injury by regulating signal transduction pathways such as Wnt,JAK-STAT, MAPK and PPAR,etc.