中文摘要：

目的研究地黄饮子（DHYZ）对APP／PSl双转基因痴呆小鼠行为学及RAGE／p38信号通路的影响。方法将20只APP／PS1双转基因痴呆小鼠随机分为模型组、DHYZ组，每组10只；另以10只同背景同月龄的C57BL／6J阴性小鼠为空白组。DHYZ组小鼠给予地黄饮子相当于生药9．75g·kg^-1·d^-1胃，模型组和空白组小鼠给予等量蒸馏水灌胃。各组灌胃30d进行Morris水迷宫空间探索实验。采用DCFH—DA法检测脑组织ROS含量，qPCR检测皮层、海马RAGE基因表达，Westernblot检测皮层、海马磷酸化p38（p-p38）蛋白表达。结果与模型组相比，DHYZ组第5天穿越平台区次数[（0．893±0．283）次]和穿越有效区次数[（1．607±0．405）次]明显增加（P〈0．05，P〈0．01），DHYZ组有效区停留距离[（23．088±7．083）cm]及时间[（1．961±1．230）S]均明显延长（P〈0．05，P〈0．01）。DHYZ组脑组织ROS平均荧光强度（122．611±7．630）降低（P〈0．01），皮层及海马RAGE基因相对表达量（1．467±0．081，7．983±0．136）均下调（均P〈0．01），皮层及海马p-p38蛋白相对表达量（0．376±0．026，0．538±0．016）下调（P〈0．01，P〈0．05）。结论DHYZ可能通过抑制RAGE／p38信号通路提高APP／PS1鼠空间探索记忆能力。

英文摘要：

Objective To investigate the effects of Dihuangyinzi （DHYZ） on behaviors and RAGE/p38 pathway in APP/PS1 mice. Method Twenty APP/PS1 dementia mice were randomly divided into model group（n= 10） and Chinese medicine group（ n= 10）. The blank group was C57 BL/6 J normal mouse（ n = 10）. The mice in Chinese medicine group were intragastric administration with DHYZ （9.75 g· kg^-1 · d^-1）. The mice in model group and blank group were treated with distilled water.After 30 days, the abilities of learning and memory of mice were detected by Morris water maze. The expression of am- yloid-betal-42（AI31-42） in the hippocampus and cortex was detected by immunohistochemistry. Reactive ox- ygen species of brain tissue were detected by DCFH-DA methods in the brain of APP/PS1 mice. Gene ex- pression level of receptor for advanced glycation end products （RAGE） was measured by real-time polymer-ase chain reaction （RT-PCR） in the cortex and hippocampus of APP/PS1 mice.The expression of phospho- mitogen-activated protein kinases （p38） was analyzed with Western blot and immunofiuorescence analysis in the cortex and hippocampus of APP/PS1 mice. Results Behavioral resuhs showed that DHYZ significantly increased the distance（（23.088±7.083） cm） and residence time（ （ 1.961± 1.230）s）of effective area in Mor- ris water maze on the fifth day（P〈0.05 ,P〈0.01 ） and remarkably increased the number of effective area cross- ings（（1.607±0.405） times） and plats（（0.893±0.283） times） in Morris water maze on the fifth day（P〈 0.01, P〈 0.05）. DHYZ also significantly reduced the intracelluar ROS level （ 122.6 I1 ± 7.630） in the brain （P〈0.01） ,and DHYZ could depress the expression of RAGE（ 1.467±0.081,7.983±0.136） and phosphoryla- tion of p38 （0.376±0.026,0.538 ± 0.016） in the cortex and hippocampus of APP/PS1 mice （P〈 0.01, P〈 0.05）. Conclusions The results demonstrate that DHYZ can partly improve memory impairment of APP/ PS1 mice by the