经前平颗粒对愤怒情绪反应模型大鼠海马基因表达谱的影响  

Effect of Jingqianping granule on gene expression profile in the hippocampus of the anger-out rat model

作　　者：郭英慧[1] 魏盛[2] 高杰[1] 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》2012年第9期1324-1328,共5页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究发展计划(973计划)资助课题(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(No 30973688);中国博士后科学基金重点资助项目(No 201003648);中国博士后基金面上项目(No 20090451343);山东省博士后创新项目专项基金资助项目(No 200803033)

摘　　要：目的在整体基因水平上探索经前平颗粒调节愤怒情绪大鼠海马基因表达谱的药物作用靶点和机制。方法采用社会隔离配合居住入侵法制备愤怒情绪反应大鼠模型,分别取正常组、愤怒模型组和经前平颗粒用药组大鼠海马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。结果芯片检测结果显示,愤怒模型组大鼠差异基因和涉及信号通路数目均较正常组多,用经前平干预后,愤怒模型组上下调差异基因数都有大幅下降。经前平颗粒可通过调节腺苷酸环化酶(Ad-cy4)、c-Jun氨基末端激酶抑制因子(TAOK3/JIK)、5-羟色胺2C受体(5-Htr2c)等多个靶基因及神经激活受体配体作用、细胞外基质受体(ECM)、MAPK及Ca2+信号等多条细胞间与细胞内信号调控途径对愤怒情绪大鼠进行干预调节。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。结论经前平颗粒通过多环节、多靶点调节优势,明显改善了愤怒情绪大鼠异常行为变化,提示经前平颗粒干预愤怒情绪大鼠的药物作用靶点和相关信号通路可作为进一步深入探讨与愤怒情绪相关的疾病发病机制的新线索。Aim To elucidate the medicine targets and molecular mechanism of Jingqianping Granule, one Chinese herbal formulae, and its effect on the gene expression in hippocampus of anger-out rat model and to identify the gene expression profile by gene-chip technique. Methods The anger-out animal models were prepared with a social isolation plus resident-intruder stress. Affymetrix rat genome 230 2.0 chips were used to analyze gene expression profiles of hippoeampus brain in control rat group, anger-out emotion rat model group and Jingqianping gran- ule treatment group. The results were analyzed by bioinformatics methods. Differential expression gene Htr3b and GABABR2 were validated by the RT-PCR test. Results Compared with normal group, the number of differential expression genes and signal pathways closely related with anger-out rat group all changed significantly. However, the numbers of differential exression genes in anger-out rat model were significantly decreased after Jingqianping granule treatment. Jingqianping improved the abnormal ethology of anger-out model rat by regula- ting genes such as Adcy4, TAOK3/JIK, 5-Htr2c,etc. and neuroactive ligand-receptor interaction, pathways such as ECM, MAPK, Calcium signal,etc. The results of RT-PCR test of Htr3b and GABABR2 gene expression were in accord with gene chips data. Conclusion Jingqianping shows significant predominance in improving the abnormal ethology of anger-out model rat by many targets and pathways. These results provide direction and clues for further diseases research on diseases that are closed related with anger-out emotion.

关 键 词：经前平颗粒 愤怒 大鼠 基因表达谱 海马 分子作 用机理 

分 类 号：R332[医药卫生—人体生理学] R286[医药卫生—基础医学]