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[海马中学习与记忆功能相关基因及六味地黄汤(LW)认知增强作用与基因表达关系的研究]

[Studies on learning and memory function-related genes in the hippocampus and the relationship between the cognitive enhancing effect of liuwei dihuang decoction (LW) and gene expression].

作者信息

Wei X L

机构信息

Beijing Institute of Pharmacology and Toxicology, Beijing 100850.

出版信息

Sheng Li Ke Xue Jin Zhan. 2000 Jul;31(3):227-30.

PMID:12545709
Abstract

Our studies showed that the expressions of the genes including glucocorticoid receptor (GR), mineralocorticoid receptor (MR), bcl-2, c-fos, neural cell adhesion molecule(NCAM), presenilin-2 (PS-2) and apoE in the hippocampus were closely related to the central learning and memory function in senescence accelerated mice (SAM), hydrocortisone(HC)-treated mice and normal mice. The differential display technique was applied to compare mRNAs expression between SAM-prone/8 (SAMP8), and SAM-resistance/1 (SAMR1). Six differentially expressed cDNA bands were identified and two of them are unknown genes. Chronic oral administration of LW (5 g/kg), a traditional Chinese medicinal prescription, significantly ameliorated the deterioration of learning and memory ability in SAMP8 and HC-treated mice and corrected the abnormal expressions of hippocampal genes. Further studies showed that corticosterone significantly affected the gene expression in primary cultured hippocampal neurons. These results suggested that central learning and memory function is closely related to the expressions of hippocampal genes. The imbalance of hypothalamic-pituitary-adrenal (HPA) axis leads to the deterioration of learning and memory function and the abnormal expressions of hippocampal genes. Therefore, one of the important ways of the cognitive enhancing effect of LW is to correct the abnormal expressions of hippocampal genes.

摘要

我们的研究表明,海马体中包括糖皮质激素受体(GR)、盐皮质激素受体(MR)、bcl-2、c-fos、神经细胞黏附分子(NCAM)、早老素-2(PS-2)和载脂蛋白E(apoE)等基因的表达与快速老化小鼠(SAM)、氢化可的松(HC)处理的小鼠及正常小鼠的中枢学习和记忆功能密切相关。应用差异显示技术比较了快速老化易感性/8(SAMP8)和快速老化抗性/1(SAMR1)之间的mRNA表达。鉴定出6条差异表达的cDNA条带,其中2条为未知基因。长期口服中药方剂六味地黄丸(LW,5 g/kg)可显著改善SAMP8和HC处理小鼠学习记忆能力的衰退,并纠正海马体基因的异常表达。进一步研究表明,皮质酮显著影响原代培养海马神经元中的基因表达。这些结果提示,中枢学习和记忆功能与海马体基因的表达密切相关。下丘脑-垂体-肾上腺(HPA)轴失衡导致学习记忆功能衰退及海马体基因异常表达。因此,LW认知增强作用的重要途径之一是纠正海马体基因的异常表达。

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