目的研究黄连解毒汤(HL)对快速老化小鼠亚系SAMP8皮层差异表达基因的影响,揭示HL对认知功能障碍的改善作用的分子机制。方法应用快速老化小鼠亚系SAMP8和SAMR1海马差异表达eDNA芯片,比较了以石杉碱甲或HL处理的SAMP8皮层基因表达谱,以及HL的药物反应基因,同时采用实时荧光定量PCR技术对芯片结果进行了验证。结果HL对SAMP8皮层基因表达具有明显的调节作用。差异表达基因有信号转导基因Dusp12,Rps6ka1,Rab26,Tat2,Phb,Syde1,Def8,Ihpk1,Pik3e2a,蛋白质代谢相关基因Tte3,Amfr,Prr6,核酸代谢基因Fhit,Itm2e,Cstf2t,能量代谢基因Stub1,Uqer,Nsf,免疫反应相关基因Clqb,转录调节基因D1ertd161e,细胞生长相关基因Ngm,Dip3b,Acrbp,递质转运相关基因skl7a7,神经系统发育相关基因Trim3,神经胶质细胞分化相关基因Tspan2,电子传递相关基因mt-Col,以及15个功能未知基因。结论HL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认知功能改善作用的;研究中发现的HL的药物反应基因可能是改善学习记忆的潜在靶标。
Objective To disclose the molecular mechanism of Huanglianjiedu Decoction (HL). enhancing the cognitive function of central nervous system, and to study the effects of HL on the genes expression in the cerebral cortex of senescence- accelerated mouse. 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 had significant regulation effects on genes in cortex of SAMP8, including genes involved in signal transduetion (Duspl2, Rps6kal, Rab26, Tac2, Phb, Syde1, DefS, Ihpkl, Pik3c2a), protein metabolism (Ttc3, Amfr, Prr6), cell growth and development (Ngrn, Dip3b, Acrbp), nucleic acid metabolism (Fhit, Itm2c, Cstf2t), energy metabolism (Stubl, Uqcr, Nsf), immune response (Clqb), regulation of transcription (Dlertdl61e), transporter (Slc17a7), nervous system development (Trim3), neurogila cell differentiation (Tspan2), electron transport (mt-Col) and 15 genes whose biological function and process were still unknown. Conclusion The effects of Huanglianjiedu Decoction on the cognitive impairments might be multiple mechanism and these genes might be the potential gene targets for impairments therapy.