经前舒颗粒对郁怒反应模型大鼠海马脑区基因表达谱的影响  

Effect of Jingqianshu granule on gene expression profile in the hippocampal of the anger-in rat model

作　　者：郭英慧[1] 高杰[1] 徐凯勇[2] 宋春红[2] 乔明琦[1] 

机构地区：[1]山东中医药大学基础医学院,山东济南250355 [2]山东中医药大学,实验动物中心,山东济南250355

出　　处：《中国药理学通报》2011年第9期1317-1321,共5页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究发展计划(973计划)资助项目(No2011CB505102);国家自然科学基金重点项目(No30930110);国家自然科学基金面上项目(No30973688);中国博士后科学基金面上资助项目(No20090451343);山东省博士后创新项目专项基金资助项目(No200803033)

摘　　要：目的在基因水平上探索经前舒颗粒对郁怒反应模型大鼠海马脑区基因表达谱影响的药物作用靶点和机制。方法采用社会隔离和居住入侵方法制备郁怒反应大鼠模型,分别取正常组、郁怒反应模型组和经前舒颗粒用药组大鼠海马脑区进行基因芯片检测和生物信息学分析。用RT-PCR方法对差异表达基因Htr3b和GABABR2进行验证。结果与正常组相比,郁药组/郁模组比较共检出127个差异表达基因,其中郁模组/正常组上调而郁药组/正常组基因下调基因有55个,郁模组/正常组下调而郁药组/正常组基因上调基因有72个,主要有各类激素受体、信号转导蛋白、代谢酶、转运蛋白、细胞因子受体等,涉及神经活化配体-受体交互作用、甘油磷脂代谢和促分裂原活化蛋白激酶等调控路径。差异表达基因Htr3b和GABABR2的RT-PCR验证结果与基因芯片数据表达的趋势一致。结论郁怒情志刺激可导致大鼠海马Htr3b、Fgfr2、Grm8、Gmeb2等较多基因的表达水平改变,经前舒颗粒通过上调或下调这些差异基因表达,进而参与神经活化配体-受体交互作用等调控路径,使郁怒反应模型大鼠行为学异常变化得到一定程度地改善,以上结果为探讨经前舒颗粒的药物作用靶点和机制提供方向和线索。Aim To elucidate the＇ medicine targets and molecular mechanism of Jingqianshu granule, one Chinese herbal formulae, on the hippocampal of anger-in rat model and to identify the gene expression profile by using gene-chip technique. Methods The angerin animal models were prepared using a social isolation plus resident-intruder stress. 230 2. 0 chips were used to profiles of hippocampus brain Affymetrix rat genome analyze gene expression in control rat group, an- ger-in emotion rat model group and Jingqianshu granule treatment group. The results were analyzed by bioinfor- matics methods. Differential expression gene Htr3b and GABAB R2 were validated by the RT-PCR test. Results Compared with normal group, 127 genes closely re- lated with anger-in were screened by detecting hippo- campus of other groups. Jingqianshu granule treatment group versus anger-in rat model, 55 and 72 genes in anger-in emotion rat model were up-regulated and down-regulated in Jingqianshu granule treatment group respectively, mainly associated with receptors of vari-ous hormones, signal transducins, metabolic enzyme, various ion channel protein, transport protein, cyto- kines receptor etc. The genes involved neuroactive lig- and-receptor interaction and MAPK signaling regulated pathways, etc. The results of RT-PCR test of Htr3b and GABABR2 gene expression were in accord with gene chips data. Conclusions The emotion responses of anger-in can lead to changes of gene expression of Htr3b, Fgfr2, Grm8, Gmeb2 etc in the hippocampus. To some extent, Jingqianshu granule can improve the abnormal ethology of model rat by up-regulating and down-regulating these genes or regulated neuroactive ligandreceptor interaction etc pathways in hippocam- pus brain of the treatment group versus angerin rat model. These results provide direction and clues for further research.

关 键 词：经前舒颗粒 郁怒 大鼠 基因表达谱 海马 分子作 用机制 

分 类 号：R-332[医药卫生] R282.71