孙伟明^1，， 王凯^1，， 郭威^1，， 毕聪聪^1，， 徐家淳^1，， 张玉莲^2，*

（  1、天津中医药大学研究生院，天津 300193；       2、天津中医药大学第二附属医院，天津 300150；  ）

摘要： 目的 探讨MAPK/ERK信号转导通路在阿尔茨海默病中的变化，以及中药女贞子有效成分齐墩果酸防治阿尔茨海默病（AD）的部分作用机制。方法 将30只雄性SD大鼠随机分为假手术组、模型组和齐墩果酸组，采用侧脑室注射聚集态β-淀粉样蛋白25-35建立AD大鼠模型。齐墩果酸组大鼠予 20mgokg-1齐墩果酸，假手术和模型组予等体积蒸馏水，各组均每日灌胃1次，共灌胃4周。采用Western blot法检测各组大鼠海马区Ras、Raf-1、B-Raf、MEK1/2、ERK1/2和p-ERK1/2蛋白表达的变化。结果 与假手术组比较，模型组Ras、Raf-1、MEK1/2、ERK1/2、p-ERK1/2表达量和p-ERK1/2与ERK1/2相对表达量比值均显著增加，B-Raf表达量显著下降，差异具有统计学意义（P＜0.05）；与模型组比较，齐墩果酸组Raf-1、MEK1/2、p-ERK1/2表达量和p-ERK1/2与ERK1/2相对表达量比值均显著下降，B-Raf表达量显著增加，差异具有统计学意义（P＜0.05）。结论 MAPK/ERK通路在AD模型大鼠脑中被过度激活，齐墩果酸可能是通过调控MAPK/ERK通路活性，从而达到治疗AD的作用。
关键词： 神经病学；齐墩果酸；阿尔茨海默病；MAPK/ERK通路；海马；蛋白

SUN Weiming^1,， WANG Kai^1,， GUO Wei^1,， BI Congcong^1,， XU Jiachun^1,， ZHANG Yulian^2,*

（  1、Graduate school,Tianjin University of Traditional Chinese Medicine,Tianjin 300193；       2、The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300150；  ）

Abstract： Objective To investigate MAPK/ERK pathway change in Alzheimer's disease, and possiable mechanism of oleanolic acid, active ingredients of traditional Chinese medicine Ligustrum lucidum, in treatment of Alzheimer's disease(AD). Method 30 SD male rats were randomly divided into 3 groups namely sham operation group, model group and oleanolic acid group, every group undergoes intragastric administration for 4 weeks and oleanolic acid group were administered oleanolic acid in accordance with 20mg/kg while the other groups were administered an equal volume of distilled water . Protein expression were detected by Western blot Results Model group increased in the expression of Ras Raf-1 MEK1/2 ERK1/2 p-ERK1/2 protein and the ratio of p-ERK1/2 to ERK1/2 while the group decreased in the expression of B-Raf protein compared with sham group. The difference was significant. Oleanolic acid group decreased in the expression of Raf-1 MEK1/2 p-ERK1/2 protein and the ratio of p-ERK1/2 to ERK1/2 while the group increased in the expression of B-Raf protein compared with model group. The difference was significant Conclusion MAPK/ERK pathway is excessively activated in rat model of AD; oleanolic acid can play a role in the treatment of AD by regulating MAPK/ERK pathway.
Keywords： Neurology; Oleanolic Acid; Alzheimer's disease; MAPK/ERK pathway; Hippocampus; Protein

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