【作者】 陈烈；

【导师】 薛俐；

【作者基本信息】 中南大学 ， 中西医结合临床， 2011， 硕士

【摘要】 目的：研究补肾活血法(益智健脑颗粒)、补肾法(地黄饮子)和活血法(血府逐瘀汤)治疗对AD模型大鼠学习、记忆能力及海马区糖原合酶激酶-3β(GSK-3β)表达的影响,从而探讨补肾活血法治疗AD的优势及部分作用机制。方法：将60只雄性SD大鼠按体重随机分为6组,分别为正常组、假手术组、模型组、补肾活血组、补肾组、活血组,每组各10只。后四组大鼠双侧海马CA1区注射p淀粉样蛋白25-35(Aβ25-35),假手术组双侧海马CA1区注射等体积的双蒸水,正常组不作任何处理。造模后补肾活血组以益智健脑浓缩液灌胃,补肾组以地黄饮子浓缩液灌胃,活血组以血府逐瘀汤浓缩液灌胃,其余3组大鼠予以等剂量双蒸水灌胃对照。造模后第21天及中药干预8周后,进行Morris水迷宫实验(Morris water maze test, MWM),最后采用半定量RT-PCR和免疫组化SP法测定大鼠海马组织中GSK-3β的表达的变化。结果：1.行为学检测结果：与其他治疗组相比,补肾活血组能有效的改善AD模型大鼠的学习、记忆能力。2. RT-PCR及免疫组化结果：与其他治疗组相比,补肾活血组AD模型大鼠脑内GSK-3β相对表达明显下调。结论：1.采用双侧海马注射Aβ25-35可建立成功的AD模型。2.补肾活血法干预可有效改善AD模型大鼠的学习、记忆能力,优于补肾法或活血法。3.补肾活血法干预后AD模型大鼠脑内GSK-3β水平明显下调,通过抑制GSK-3β的活性可降低Tau蛋白的异常高度磷酸化水平,防止Ap在神经元外大量沉积,且优于补肾法或活血法。更多还原

【Abstract】 Objective:To investigate the effects of Bushen Huoxue(Yizhi Jiannao granule) method、Bushen(Decoction of Rehmanniae granule) method and Huoxue (Xuefu Zhuyu granule) method decoction’s on Alzheimer’s disease model rats’ learn and memory ability and the expression of GSK-3βin hippocampus, this work discusses partially the mechanism and preponderance of traditional Bushen Huoxue method to treat Alzheimer’s disease.Methods:60 SD male rats were randomly divided into six groups by weight, normal group, sham controls group, model group, Bushen Huoxue group, Bushen group, Huoxue group, and various groups of 10 only. The last Four groups injects beta amyloid protein 25-35 (Aβ25-35) in bilateral hippocampal CA1 region, sham controls group injection steam water, normal group received no special treatment. The Bushen Huoxue group、Bushen group and Huoxue group are gavaged separately Yizhi Jiannao granule、Decoction of Rehmanniae granule and Xuefu Zhuyu granule, the other theree group are gavaged such equal dose double-distilled water. And after operation 21 days and Chinese medicine therapy eight weeks, carry out MWM(morris water maze test) behavior detection.Last,the hippocampal of rats were taken out to examine the expression of GSK-3βby semi-quantitative RT-PCR and immunohistochemistry SABC method.Results:1. Behavioral results:compared with other treatment group, the Bushen Huoxue group can effectively improve AD of rats’ ability to learn and remember.2. RT-PCR and immunohistochemical result:compared with other treatment group, the Bushen Huoxue group can effectively reduce the level of GSK-3βin the AD mice model.Conclusion:1. Bilateral hippocampal injection by Aβ25-35 can build successful AD model.2. The Bushen Huoxue method can effectively improve learn and memory ability in the AD mice model, superior to Bushen group or Huoxue group.3. After the Bushen Huoxue method therapy, the level of GSK-3pin the AD mice model were decreased, by inhibiting through GSK-3βactivity can reduce the phosphorylated proteins abnormal high level of Tau beta, prevent Aβin neurons, superior to Bushen group or Huoxue group.更多还原