当归芍药散和调心方对快速老化模型小鼠海马和皮层基因表达的影响
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摘要
以阿尔茨海默病(Alzheimer's disease，AD)为代表的神经退行性疾病已成为严重危害人类健康的四大杀手疾病之一。而海马和皮层是学习记忆的中枢。本研究采用快速老化模型小鼠海马差异表达cDNA芯片筛选了DSS和TXF对SAMP8海马和皮层基因表达的影响，结果表明，DSS和TXF对SAMP8海马和皮层基因的表达皆具有显著的影响，其影响既有相同之处，又有不同之处。其不同之处与其不同的作用靶点、作用性质和机理具有密切关系；其相同之处则提示二者之间可能存在相同的药理作用环节或靶点。这些基因包括：线粒体功能相关基因18S rRNA、S21和Rn18s；线粒体功能相关基因MTCO1、UQCRFS1和mitochondrial 12S ribosomal RNA；物质转运功能相关基因BNPI、AMF-R和Trim3：信号传导功能相关基因Rps6ka1、Tenc1、DUSP12、Rab26和Map4k6-pending；细胞周期相关基因Fhit和GANP；物质代谢功能相关基因STUB1和UBE2D2；DNA修复功能相关基因ERCC5；转录功能相关基因SSU72和细胞骨架相关基因Dync1h1；核蛋白基因PRR6；免疫功能相关基因Mink；膜蛋白基因Itm2c：神经元分化相关基因Mib等，以及大量未知功能基因和未测序克隆。通过荧光实时定量RT-PCR验证及经数据库检索和文献调研，这些基因中许多与海马和皮层某种功能密切相关，提示这些基因与DSS、TXF改善SAMP8学习记忆或认知功能具有密切关系，因此，有理由认为，在所发现的DSS、TXF反应基因中，可能存在可用于防治AD药物筛选和研究的潜在基因靶标，从而为进一步深入研究AD的发病机制和筛选AD药物的作用靶标提供了条件和手段，打下了良好的基础。
Alzheimer's disease (AD) is one of the most prevalent progressive, neurodegenerative diseases, which primarily affects the elderly population.This paper found many differential expression genes in the hippocampus and cortex of SAMP8 after administrated with DSS and TXF, These genes include: mitochondrial gene, S21 Rn18s and 18S; ribosome gene MT0C1, UQCRFS1 and mitochondrial 12S ribosomal RNA; substance metabolism gene STUB1 and UBE2D2; material transduction gene BNPI, AMF-R and Trim3; and signal transduction gene Rps6kal, Tend, DUSP12, Rab26 and Map4k6-pending; DNA replication gene Fhit and GANP; substance metabolism gene STUB1, UBE2D2; DNA repair gene ERCC5; transcription gene Ssu72; cystoskeleton gene Dynclh1; immune gene Mink; membrane protein gene Itm2c; neuron differentiation gene Mib and lots of function unknown genes and un-sequenced clones. Then, 4 of these genes were identified by QRT-PCR. These genes are closely related with some functions of hippocampus and cortex. It suggests those genes are related with the learning and memory deficient or pathology change in brain of SAMP8. They are potential gene targets of drugs to therapy AD.
Alzheimer's disease (AD) is one of the most prevalent progressive, neurodegenerative diseases, which primarily affects the elderly population.This paper found many differential expression genes in the hippocampus and cortex of SAMP8 after administrated with DSS and TXF, These genes include: mitochondrial gene, S21 Rn18s and 18S; ribosome gene MT0C1, UQCRFS1 and mitochondrial 12S ribosomal RNA; substance metabolism gene STUB1 and UBE2D2; material transduction gene BNPI, AMF-R and Trim3; and signal transduction gene Rps6kal, Tend, DUSP12, Rab26 and Map4k6-pending; DNA replication gene Fhit and GANP; substance metabolism gene STUB1, UBE2D2; DNA repair gene ERCC5; transcription gene Ssu72; cystoskeleton gene Dynclh1; immune gene Mink; membrane protein gene Itm2c; neuron differentiation gene Mib and lots of function unknown genes and un-sequenced clones. Then, 4 of these genes were identified by QRT-PCR. These genes are closely related with some functions of hippocampus and cortex. It suggests those genes are related with the learning and memory deficient or pathology change in brain of SAMP8. They are potential gene targets of drugs to therapy AD.
引文
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