栀子苷、胆酸及其配伍干预脑缺血全基因表达谱的比较研究  

Comparative study on effects of jasminoidin, ursodeoxycholic acid and their combination on gene expression in brain of mice with cerebral ischemia

作　　者：荆志伟[1] 张亮[2] 王忠[1] 张占军[3] 胡木林[1] 程京[2] 李澎涛[4] 高思华 王永炎[1] 

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京100700 [2]生物芯片北京国家工程研究中心 [3]北京师范大学认知神经科学与学习国家重点实验室 [4]北京中医药大学基础医学院 [5]国家中医药管理局科技司

出　　处：《北京中医药大学学报》2007年第7期462-467,I0004,共7页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家"十一五"科技支撑计划资助项目(No.2006BAI08B04-06)

摘　　要：目的比较脑缺血后清开灵主要组分栀子苷、胆酸及其配伍对基因表达谱的影响。方法建立全脑缺血再灌注小鼠模型,分为栀子苷组、胆酸组、栀子苷+胆酸组。一步法抽提小鼠脑组织的总RNA,Cy3/Cy5标记,16463个小鼠脑oligo片段芯片检测全基因组表达谱,每组重复实验669次。Genespring分析显著变化基因,GO原则分类,层次聚类分析全基因组表达谱信息。结果栀子苷组、胆酸组、栀子苷+胆酸组所致差异表达基因数分别为95、86、102,其中上调63、48、56个,下调32、38、45个基因,共同调节基因19个。3组差异基因集中在代谢和信号转导相关基因方面。重叠基因数栀子苷+胆酸组与胆酸组(30个)多于栀子苷+胆酸组与栀子苷组(25个),前两者及早反应基因如Pip92表达相似,后两者则在炎症相关因子,如NFκB、Irf5、IL-1β、TNF-α、IL-6、IFN-γ等表达雷同;聚类分析发现栀子苷组表达谱较胆酸组更接近栀子苷+胆酸组;实时定量PCR结果与芯片结果一致。结论①虽然栀子苷组、胆酸组与栀子苷+胆酸组存在共同的调节基因,但栀子苷组偏重于对炎症相关因子,特别是对NFκB、Irf5等炎症介导因子的调控;而胆酸组对Pip92等凋亡前功能基因的调节较为突出;②重叠基因数与聚类分析结果的不一致提示基因分析不能仅局限在差异数量上,而应该深入分析基因功能和组分的关系。Object To compare the effects among jasminoidin, ursodeoxycholic acid and their combination on gene expression in the brain of mice with cerebral ischemia-reperfusion injury. Methods The model mice with whole cerebral ischemia- reperfusion were divided into Group Jasminoidin （JA）, Group Ursodeoxycholic Acid（UA） and Group JA ＋ UA（JU）. Total RNA was abstracted by the method of One Step from the brains of experimental mice. Labeled by Cy3/CyS, all samples were tested in gene expression profile by oligo genechip with 16,463 mice brain gene group. According to GO principle, Genespring software fragments. The test was repeated 6-9 times in every was used to analyze significantly expressed genes, and global genomic information was analyzed by hierarchical clustering. Results The significantly expressed genes in Group JA, UA and JU were 95, 86 and 102 respectively, including 63, 48 and 56 upregulated genes and 32, 38 and 45 down -regulated ones as well as 19 common regulation genes. Three groups of differently expressed genes were related with metabolism and signal transportation. The overlap genes of group JU and UA（30） was more than that of JU and JA（25）, but the former had similar results of early growth response gene, and the latter on inflammation relative genes such as NF-κB, IrfS, IL-1β, TNF-α, IL-6, IFN- γ and so on. Cluster analysis showed gene expression profile of JA was more proximate with JU than that of UA. Real-time PCR results were consistency to genechip results. Conclusions （a） Though there are many common regulation genes among JA, UA and JU, JA has more effects on inflammation relative genes, especially on mediated gene such as NF-κB, IrfS, while UA has more adjustableeffects on pre-apoptosis functional genes such as Pip92; （b） The discordance between quantity analysis and cluster analysis suggests that not only significant expression genes have quantity difference, but also the relation between gene functions and components should be studied further.

关 键 词：栀子苷 胆酸 组分配伍 脑缺血 基因芯片 层次聚类 

分 类 号：R285.5[医药卫生—中药学]