六味地黄汤对快速老化小鼠海马差异表达基因的影响

The effects of Liuwei Dihuang decoction on the differential expression genes in the hippocampus of senescence-accelerated mouse

目的研究六味地黄汤(LW)对快速老化小鼠(senescenceacceleratedmouse,SAM)海马差异表达基因的影响,揭示LW增强认知功能的分子作用机制。方法应用快速老化小鼠亚系SAMP8和SAMR1海马差异表达cDNA芯片,比较SAMP8和SAMR1、SAMP8阴性对照和SAMR1阳性对照、石衫碱甲处理的SAMP8和SAMP8阴性对照以及LW处理的SAMP8和SAMP8阴性对照8个基因表达谱,并对LW的药物效应基因进行比较。结果给予SAMP8LW后,基因DUSP12、NSF、STUB1、CAMKⅡα、AMFR、UQCRFS1和11个新基因的表达出现显著差异,这些基因涉及蛋白酪氨酸磷酸酶家族、苏氨酸/丝氨酸蛋白激酶家族、泛素连接酶和线粒体功能等,LW对SAMP8海马的基因表达具有明显的调控作用。结论提示LW作用于认知功能也许是通过维持正常的细胞增殖和分化、保护正常的突触传递、调节Ca2+信号转导、改善线粒体的功能等途径实现的,基因DUSP12、NSF、STUB1、CAMKⅡα、AMFR、UQCRFS1和11个新基因可能是LW改善学习记忆功能的潜在作用靶标。

Aim To disclose the molecular mechanism of Liuwei Dihuang decoction （LW） enhances the cognitive function of central nervous system, the effects of Liuwei Dihuang decoction on the differential expression genes in the hippocampus of senescence-accelerated mouse was studied. Methods There were 8 gene expression patterns, such as SAMP8 and SAMR1, SAMP8 as negative control and SAMR1 as positive control, huperzine A-treated SAMP8 and SAMP8 as negative control, LW-treated SAMP8 and SAMP8 as negative control, were compared and assessed by use of the differential expression cDNA microarray of the hippocampus of SAMP8 and SAMR1. The response genes of LW were compared. Results LW had significant modulating effects on some of the gene expressions.Expressions of genes, such as DUSP12, NSF, STUB1, CaMK Ⅱα, AMFR, UQCRFS1 and other 11 novel genes without any functional clues changed significantly. These genes involved in the protein-tyrosine phosphatase family, the AAA （ATPases associated with diverse cellular activities）gene family, the serine/threonine protein kinases family, ubiquitin ligase, mitochondrial function and so on. Conclusions These resuits suggested LW effects on the cognitive impairments might be multi-mechanism and these genes might be the potential gene targets for LW effects on the impairments.