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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。
Objective To investigate the effect of modified wuzi-yanzong prescription (MWP) on whole brain gene expression profiles of senescence accelerated mouse-prone / 8 (SAMP8) mice in order to investigate the effects of modified Wuzi Yanzong prescription on dementia Related mechanisms of disease. Methods Six SAMP8 presenile dementia mice were randomly divided into model group and Jiawei Wuzi Yanzong decoction group, and three control mice SAMR1 (SAMR1) served as blank control group blank group. The rats in the Jiawei Wuzi Yanzong group were given gavage for 9 g · kg-1 · d-1, and the rats in the blank group and the model group were fed with the same volume of sodium carboxymethyl cellulose (CMC- Na). After 10 days, the whole brain was removed for genome-wide expression profiling. Results Compared with the model group, there were 293 differentially expressed genes in the modified Wuzi Yanzong group, including 179 up-regulated genes and 114 down-regulated genes. Seventeen key targets involved in neural stem cell proliferation and differentiation include gene ontology (GO) analysis and KEGG database analysis, including Notch pathway, Rap1 / B- There are 9 key targets involved in the regulation of the Raf / ERK pathway and related target proteins in neuronal-endocrino-immune (NEI) networks, including follicle stimulating hormone (FSH), luteinizing hormone luteinizing hormone (LH), prolactin, thyroid stimulating hormone (TSH) and the like. Conclusion The mechanism of Jiawei Wuzi Yanzong Recipe on the brain of dementia mice with SAMP8 may involve in the proliferation and differentiation of neural stem cells and the regulation of NEI network.