复方地黄对AD大鼠学习记忆及Wnt通路相关蛋白表达的影响  

Effects of Compound Rehmanniae Radix on Learning and Memory Ability and Expression of Wnt Passway Associated Proteins in Hippocampus of Rats with Alzheimer's Disease

作　　者：姚宏波[1] 王月静[1] 廉洁[1] 张萌[1] 孙丽慧[1] 

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006

出　　处：《中国实验方剂学杂志》2016年第13期107-111,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：齐齐哈尔市科技局项目(SFGG-201409)

摘　　要：目的:观察复方地黄对阿尔茨海默病(AD)模型大鼠学习记忆及Wnt通路相关蛋白表达的影响,探讨其作用机制。方法:采用Morris水迷宫筛选出健康Wistar大鼠,随机分为正常组,模型组,复方地黄高、低剂量(3.37,1.35 g·kg-1)组,加兰他敏(0.6 mg·kg-1)组。双侧海马区注射β-淀粉样蛋白(Aβ)23-35造模(每侧10μL),注射后第9天,ig相应药物,持续30d。采用水迷宫检测大鼠的学习记忆能力,用免疫组化、免疫印迹及实时荧光定量PCR检测大鼠海马Wnt通路相关蛋白轴蛋白(Axin)及细胞周期蛋白(Cyclin D1)表达。结果:模型组大鼠逃避潜伏期和首次到达原平台象限的时间均较正常组显著增多(P<0.01)。与模型组比较,加蓝他敏组及复方地黄高、低剂量组大鼠逃避潜伏期和首次到达原平台象限的时间明显减少(P<0.05)。复方地黄高剂量组较加兰他敏组首次到达原平台象限的时间减少(P<0.05)。免疫组化结果显示阳性表达Axin在胞质,Cyclin D1在胞核。免疫印迹法及实时荧光定量PCR结果显示,与正常组大鼠比较,模型组大鼠海马Axin mRNA及蛋白表达显著增高(P<0.01);与模型组比较,复方地黄高、低剂量组及加兰他敏组大鼠海马Axin mRNA及蛋白表达明显降低(P<0.05),Cyclin D1mRNA及蛋白表达明显升高(P<0.05)。结论:复方地黄可以改善AD模型大鼠学习记忆能力,其作用机制可能与降低AD大鼠海马Wnt通路相关蛋白Axin,增强Cyclin D1表达密切相关。Objective： To observe the effects of compound Rehmanniae Radix on learning and memory abilities,as well as expressions of Wnt pathway associated proteins in Alzheimer＇s disease（ AD） model rats.Method： The 60 healthy Wistar rats were screened by Morris water maze,and randomly divided into 5 groups：normal group, model group, compound Rehmanniae Radix low does（ 1. 35 g · kg^-1） group,compound Rehmanniae Radix high does（ 3. 37 g·kg^-1） group and galanthamine（ 0. 6 mg·kg^-1） group,n = 12 in each group. The AD models were induced by injecting Aβ23-35 in the bilateral hippocampus,10 μL for each side at one time. On 9thday after injection of Aβ23-35,the rats in compound Rehmanniae Radix groups and galanthamine group were given with corresponding medicines by intragastric administration for a course of 30 days. The water maze test was used to evaluate the learning and memory ability in rats,the positioning and quantitative expressions of Wnt pathway associated proteins（ Axin） and cell cycle proteins（ Cyclin D1） in hippocampus were detected by immunohistochemisty,Western blot and Real-time PCR. Result： As compared with the normal group,the escape latency and the time to first reach the original platform quadrant were significantly more in model group（ P 0. 01）. As compared with the model group,the escape latency and the time to first reach the original platform quadrant were significantly reduced in galanthamine group and compound Rehmanniae Radix groups（ P〈 0. 05）.As compared with galanthamine group,the time to first reach the original platform quadrant was reduced in compound Rehmanniae Radix high dose group（ P 〈0. 05）. Immunohistochemisty results showed that,positive expression was in cytoplasm for Axin and in nucleus for Cyclin D1. Western blot and Real-time PCR test results showed that,as compared with the normal group,the protein and mRNA expression levels of Axin in hippocampus were significantly increased in the model group（ P 〈0. 01）,as compared with th

关 键 词：阿尔茨海默病 复方地黄 WNT 轴蛋白 细胞周期蛋白 

分 类 号：R285.5[医药卫生—中药学]