黄连解毒汤对快速老化小鼠海马基因表达的影响

The Effects of Huang-Lian-Jie-Du Decoction on the Gene Expression in the Hippocampus of Senescence-Accelerated Mouse

目的:研究黄连解毒汤(HL)对快速老化小鼠亚系SAMP8海马差异表达基因的影响,揭示HL改善认知功能障碍的分子机制。方法:应用快速老化小鼠亚系SAMP8和SAMR1海马差异表达cDNA芯片,比较了SAMP8和SAMR1、石杉碱甲处理的SAMP8和SAMP8对照,以及HL处理的SAMP8和SAMP8对照的基因表达谱,并对HL的药物反应基因进行了比较;采用实时荧光定量PCR技术对芯片结果进行了验证。结果:给予SAMP8 HL后,对SAMP8海马基因表达具有明显的调节作用。差异表达基因包括信号转导基因Dusp12、Rps6ka1、Penk1、Nope,Leng8,蛋白质代谢相关基因Ttc3、Amfr、Prr6、Ube2d2,核酸代谢基因Fhit、Itm2c、Cstf2t、Ddx3x、Ercc5、Pcgfr6,能量代谢基因Stub1,免疫反应相关基因C1qb,转录调节基因D1ertd161e、Gcn5l2、Ssu72,细胞生长相关基因Ngrn、Anln,递质转运相关基因Slc17a7,以及功能未知基因12个。结论:提示HL对于认知功能的改善可能是通过调节信号转导、突触传递、蛋白质和能量代谢、细胞增殖分化等途径发挥作用的;研究中发现的HL作用基因可能是改善学习记忆的潜在靶标。

Objective： To disclose the molecular mechanism of Huang-Lian-Jie-Du decoction（HL） enhancing the cognitive function of central nervous system, the effects of HL on the genes expression in the hippocampus of senescence-accelerated mouse were studied. Methods： The gene expression patterns, including SAMP8 vs SAMR1, SAMP8 treated with huperzine A vs SAMP8 control, SAMP8 treated with HL vs SAMP8 control, were performed using the cDNA microarray. Results： HL showed significant regulation effects on genes in hippocampus of SAMP8, including genes involved in signal transduction（Duspl2, Rps6kal, Penkl, Nope, Leng8）, protein metabolism（Ttc3, Amfr, Prr6, Ube2d2）, cell growth and development（Ngrn, Anln）, nucleic acid metabolism（Fhit, ltm2c,Cstf2t, Ddx3x, Ercc5, Pcgfr6）, energy metabolism（Stub1）, im- mune response（ Clqb ）, regulation of transcription（Dlertdl61e, Gcn512, Ssu72）, transporter（Slcl7a7）, and 12 genes whose biological function and process were still unknown. Conclusion： These results suggested that HL＇s effects on the cognitive impairments might be multiple mechanism and these genes might be the potential gene targets for impairments therapy.