海马学习记忆功能有关基因及六味地黄汤益智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

运用逆转录 多聚酶链反应 (RT PCR)技术及学习记忆行为实验 ,通过快速老化模型小鼠 (SAM )、氢化可的松处理小鼠及正常小鼠 ,研究发现海马糖皮质激素受体 (GR)、盐皮质激素受体 (MR)、bcl 2、c fos、神经细胞粘附分子 (NCAM )、早老蛋白 2 (PS 2 )及apoE与中枢学习记忆功能具有密切的关系。应用mRNA差异显示技术研究发现 ,SAM的快速老化亚系SAMP8和抗快速老化亚系SAMR1海马有 6条明显差异的基因片段 ,其中二个为新基因。口服六味地黄汤 (LW )对模型动物学习记忆功能衰退具有明显的改善作用 ,同时对海马基因表达异常具有明显纠正作用。应用胚胎大鼠原代培养的海马神经元研究发现皮质酮对学习记忆有关基因表达具有明显影响。上述结果提示 ,中枢学习记忆过程与海马多种基因表达存在密切的关系 ,纠正海马基因表达异常、调节下丘脑 垂体 肾上腺 (HPA)轴的平衡是LW益智作用的重要机制之一。

Our studies showed that the expressions of the genes including glucocorticoid receptor (GR), mineralocorticoid receptor (MR), bcl 2, c fos, neural cell adhesion [CM(36]molecule (NCAM), presenilin 2 (PS 2) and apoE in the hippocampus were closelyrelated 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.