文献类型：期刊文献

中文题名：黑逍遥散对阿尔茨海默病大鼠海马基因表达谱的影响

英文题名：Effect of Heixiaoyao Powder on Hippocampal Gene Expression Profile of Alzheimer's Disease Rats

作者：吴红彦[1,2];李海龙[1,2];顾静[1,2];杨植媛[1];王虎平[1,2];车敏[1];兰美华[3]

第一作者：吴红彦

机构：[1]甘肃中医药大学基础医学院方剂学教研室,兰州730000;[2]甘肃省中医方药与创新转化实验室,甘肃省中药新产品创制工程实验室,兰州730000;[3]广东省阳江市中医院内三科,广东529500

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2016

卷号：36

期号：11

起止页码：1345

中文期刊名：中国中西医结合杂志

外文期刊名：Chinese Journal of Integrated Traditional and Western Medicine

收录：CSTPCD;;Scopus;北大核心:【北大核心2014】；CSCD:【CSCD2015_2016】；PubMed;

基金：国家自然科学基金资助项目(No.81060284)

语种：中文

中文关键词：黑逍遥散;阿尔茨海默病;基因表达谱;锌指蛋白;wnt信号通路

外文关键词：Heixiaoyao Powder; Alzheimer＇s disease; gene expression profile; zinc finger protein; wnt signal pathway

摘要：目的观察黑逍遥散对Aβ25-35诱导阿尔茨海默病(Alzheimer's disease,AD)大鼠模型海马基因表达谱的影响。方法选择雌性SD大鼠,以海马注射Aβ25-35淀粉样蛋白建立AD模型,并设立假手术组、模型组、西药组及中药高、中、低剂量组,每组14只。大鼠造模7天后连续灌胃[3 m L/(kg·d)]28天,假手术组与模型组给予生理盐水,西药组给予石杉碱甲片水溶液[0.02 mg/(kg·d)],中药高、中、低剂量组分别给予黑逍遥散水煎液[17.00、8.50、4.25 g/(kg·d)]。灌胃结束后处死大鼠解剖取得大鼠海马组织,并提取组织RNA,利用大鼠基因表达谱芯片筛选差异表达的基因,而后对获得的部分剂量依赖性变化的差异表达基因进行qRT-PCR验证。结果与假手术组比较,模型组583个基因表达上调,579个下调,wisp1、crebbp、igfbp-1、znf483、zfp37及zic4 mRNA表达升高,casq2、bcl-2 mRNA表达降低(P<0.05)。与模型组比较,中药高、中、低剂量组276个基因表达上调,170个下调,其中71个基因剂量依赖性上调表达,70个基因剂量依赖性下调表达,西药组igfbp-1、znf483、zfp37及zic4 mRNA降低,casq2、bcl-2 mRNA升高(P<0.01);中药高剂量组wisp1、crebbp、igfbp-1、znf483、zfp37及zic4降低(P<0.01),casq2、bcl-2 mRNA升高(P<0.01);中药中剂量组crebbp、igfbp-1、znf483、zfp37及zic4降低(P<0.01,P<0.05),casq2、bcl-2 mRNA升高(P<0.01,P<0.05);中药低剂量组igfbp-1、znf483、zfp37及zic4 mRNA降低(P<0.01)。与中药高剂量组比较,中药中剂量组crebbp、zfp37、zic4 mRNA升高(P<0.01),igfbp-1、bcl-2 mRNA降低(P<0.01,P<0.05);中药低剂量组crebbp、znf483、zfp37 mRNA升高(P<0.01,P<0.05),igfbp-1、bcl-2、zic4 mRNA降低(P<0.01)。与中药中剂量组比较,中药低剂量组casq2、bcl-2、zic4 mRNA降低(P<0.01,P<0.05)。结论黑逍遥散可通过调控zfp37、znf483、zic4表达影响AD发生;通过抑制wnt信号通路相关基因wisp-1、crebbp、igfbp-1、casq2的表达而影响Aβ代谢和Tau蛋白异常磷酸化。
Objective To observe the effect of Heixiaoyao Powder （HP） on gene microarray pro- file of hippocampus in Aβ25-35 fragments induced Alzheimer＇s disease rat model. Methods Female SD rats were chosen to establish AD model by injecting Aβ25-35 amyloid into hippocampus ,and then they were divid- ed into 6 groups, i.e., the sham-operation group, the model group,the Western medicine （WM） group, high, middle, and low dose HP groups, 14 in each group. After 7 days of modeling, all rats were adminis- tered with respective solution at the daily dose of 3 mL/kg by gastrogavage for 28 successive days. Normal saline was administered to rats in the sham-operation group and the model group. Huperzine A Tablets wa- ter solution was administered to rats in the WM group at the daily dose of 0.02 mL/kg. HP at the daily dose of 4.25, 8.50, 17.00 g/kg was administered to rats in the low, middle, high HP groups. All rats were sacri- ficed after ending gastrogavage, and their hippocampal tissues were collected to extract tissue RNA. Rat gene microarray was used to screen differentially expressed genes, and then differentially expressed genes with partial dose-dependently changing obtained by microarry were verified by qRT-PCR. Results Compared with the sham-operation group, 538 genes were up-regulated, and 579 genes were down-regula- ted in the model group, mRNA expressions of wisp1, crebbp, igfbp-1, znf483, zfp37, and zic4 increased, while mRNA expressions of casq2 and bcl-2 decreased in the model group （P 〈0.05）. Compared with the model group, 276 genes were up-regulated, and 170 genes were down-regulated in the 3 HP groups. Of them, 71 up-regulated genes dose-dependently and 70 down-regulated genes dose-dependently, mRNA ex- pressions of igfbp-1, znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 in- creased in the WM group （P 〈0.01 ）. mRNA expressions of wisp1, crebbp, igfbp-1, znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 increased in the high dose HP group （P 〈0.01 ）. mRNA expressions of crebbp, igfbp-1, znf483, zfp37, and zic4 decreased （P 〈0.01, P 〈0.05）, while mR- NA expressions of casq2 and bcl-2 increased in the middle dose HP group （P 〈0.01, P 〈0.05）. mRNA ex- pressions of igfbp-1, znf483, zfp37, and zic4 decreased in the low dose HP group （P 〈0.01 ）. Compared with the middle dose HP group, mRNA expressions of crebbp, zfp37, and zic4 increased （P 〈0.01 ）, mR- NA expressions of igfbp-1 and bcl-2 decreased in the middle dose HP group （P 〈0.01, P 〈0.05） ; mRNA expressions of crebbp, znf483, and zfp37 increased （P 〈0.01, P 〈0.05）, mRNA expressions of igfbp-1, zic4, and bcl-2 decreased in the low dose HP group （P 〈0.01 ）. Compared with the middle HP group, mRNA expressions of casq2, zic4, and bcl-2 decreased in the low dose HP group （P 〈0.01, P 〈0.05）. Conclusion HP could affect the occurrence of AD by regulating mRNA expressions of zfp37, znf483, and zic4, and af- fect the metabolism of AI3 and abnormal phosphorylation of Tau protein by inhibiting wnt signal pathway re- lated genes such as wisp-l, crebbp, igfbp-1, and casq2.