目的 研究加味五子衍宗方(modified wuzi-yanzong prescription, MWP)对早老化痴呆小鼠SAMP8(senescence accelerated mouse-prone/8, SAMP8)全脑基因表达谱的影响,以探究加味五子衍宗方治疗痴呆性疾病的相关作用机制。方法 6只SAMP8早老化痴呆小鼠随机平均分为模型组(model group)和加味五子衍宗方处理组,3只正常对照小鼠SAMR1(senescence accelerated mouse-resistance/1, SAMR1)作为空白对照组(blank group),加味五子衍宗方组连续灌胃加味五子衍宗方 9 g·kg-1·d-1,空白组和模型组灌胃同体积羧甲基纤维素钠(sodium carboxyl methyl cellulose, CMC-Na),10 d后取出全脑,进行全基因组表达谱分析。结果 与模型组比较,加味五子衍宗方组筛选出293个差异基因,其中上调基因179个,下调基因114个。基因本体论(gene ontology, GO)分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)数据库分析涉及神经干细胞增殖分化的关键靶点有17个,包括Notch通路、Rap1/B-Raf/ERK通路、以及相关靶标蛋白,涉及神经-内分泌-免疫(neuro-endocrino-immune, NEI)网络调控的关键靶点有9个,包括促卵泡激素(follicle stimulating hormone, FSH),黄体化激素(luteinizing hormone, LH),催乳素通路(prolactin),促甲状腺激素通路(thyroid stimulating hormone, TSH)等。结论 加味五子衍宗方对SAMP8早老化痴呆小鼠大脑影响机制涉及神经干细胞增殖分化和NEI网络调控。
Abstract
OBJECTIVE To study the effect of modified wuzi-yanzong prescription(MWP) on brain gene expression profile in senescence accelerated mouse-prone/8(SAMP8) mice and detect the mechanism of MWP treating dementia-related diseases. METHODS Six SAMP8 mice were randomly divided into model group and MWP group on average, meanwhile three senescence accelerated mouse-resistance/1(SAMR1) mice were chosen as the blank control group. The MWP group was intragastrically intervened by MWP 9 g·kg-1·d-1, while model group and control group were given equal volume of sodium carboxyl methyl cellulose, once a day. After 10 d, the mice in experiment were killed and separated the whole brain. Brain RNA expression was analyzed using Illumina whole genome expression profiles. RESULTS Compared with the model group, 293 differential genes were screened in the MWP group, including 179 up-regulated genes and 114 down-regulated genes. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated 17 key targets about differentiation and proliferation of neural stem cells, including Notch pathway, Rap1 / B- Raf/ERK pathway and related target proteins; 9 key targets about neural endocrine-immune (NEI) network, including follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid stimulating hormone(TSH), etc. CONCLUSION The action mechanisms of MWP on brain in SAMP8 mouse involve the regulation of proliferation and differentiation of neural stem cells and NEI network.
关键词
基因芯片 /
加味五子衍宗方 /
SAMP8小鼠 /
神经干细胞 /
神经-内分泌-免疫网络系统
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Key words
gene microarray /
modified wuzi-yanzong prescription /
SAMP8 mice /
neural stem cell /
neural endocrine-immune network
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中图分类号：
R965
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参考文献
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脚注
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基金
国家自然科学基金面上项目(81173369,81303253);北京市自然科学基金面上项目(7132210);教育部博士点基金资助项目(20120001110105)
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