二苯乙烯苷对D-半乳糖拟痴呆小鼠海马基因表达的影响

Effect of 2,3,5,4′-tetrahydroxystilbene-2-o-β-D-glucoside on hippocampal genes expression in mimetic-dementia mice induced by D-galactose

目的 应用cDNA芯片探索二苯乙烯苷(TSG)干预D 半乳糖皮下注射的拟痴呆 (AD)小鼠海马的靶基因。方法 D 半乳糖 (5 0mg·kg- 1·d- 1,6 0d)皮下注射为模型组 ,造模加TSG (0 .1g·kg- 1·d- 1)灌胃为TSG组 ,对照组只注射相同体积的生理盐水。每组 6只小鼠用Morris水迷宫测试学习记忆能力。取海马组织抽提RNA ,掺入荧光分子Cy3和Cy5逆转录合成cDNA探针。以模型比正常组和TSG比正常组为组合混合探针 ,与两张小鼠 4 0 0 0点cDNA芯片杂交 ,经荧光信号扫描及GenePixPro3.0分析TSG组AD疾病相关基因调控得到改善的基因。结果 TSG可缩短小鼠游至目标的距离和时间 ,说明改善了学习记忆能力。TSG组与模型组表达差异的基因有 2 9条上调 ,12条下调 ,其中与AD相关的有 11条。结论 基因表达结果说明 ,TSG可能使能量代谢与神经营养作用增强 ,炎性反应和转录整体水平下降。

AIM To explore the mechanism of the action o f 2,3,5,4′-tetrahydroxystilbene-2-o-β-D-glucoside (TSG) on mimetic dementia mice. METHODS Three months old mice were divided into three groups: control (saline sc and ig), D-galactose (50 mg·kg -1·d -1 sc) plus saline (ig), and D-galactos e (50 mg·kg -1·d -1 sc) plus TSG (0.1 g·kg -1·d -1 ig). After treatment for 60 d, each group of six mice was tested by Morris water maz e and the total RNA of each group′s hippocampal tissue in equiponderant weight were isolated by TRIZOL agent. The mRNA of control group was reversely tr anscribed to cDNA by using Cy5-dUTP, while mRNA of D-galactose and TSG group was reversely transcribed by using Cy3- dUTP. The mixture of control and D-galactose group cDN A probes were hybridized with gene chip consisted of 4000 genes, and the mixture of control and TSG group cDNA probes were hybridized with the the same kind of gene chip. The fluorescent signals of gene chip were analyzed by GenePixPro 3.0 system. RESULTS Compared with the D-galactose group, the expression of 41 genes from TSG group varied differently and seemed to trend to that of control group. Among 41 genes, 29 genes were up-regulated and 12 genes were down-regulated. CONCLUSION After the intervent io n of TSG, some genes′ expression in mouse hippocampus seemed to be improved. Th ese genes are related to energy metabolizing, inflammatory reaction, nerve growt h-related factors and total genes transcription level.