【作者】 王慧玲；

【导师】 董克礼；

【作者基本信息】 中南大学 ， 中西医结合临床， 2008， 硕士

【摘要】 目的:研究益智健脑颗粒对快速老化模型小鼠SAMP8海马肽基脯氨酰顺反异构酶(Pin1)与高迁移率族蛋白B1(HMGB1)mRNA表达的影响,从而探讨中药益智健脑颗粒防治阿尔茨海默病(AD)的部分作用机理。方法:6月龄快速老化模型小鼠SAMP8进行行为学检测后,随机分为中药治疗组和模型组,6月龄正常老化小鼠SAMR1作为正常对照组。中药组以益智健脑颗粒浓缩液灌胃,正常对照组和模型组以同体积的蒸馏水灌胃。8周后,采用半定量RT-PCR检测海马组织中Pin1、HMGB1 mRNA的表达。结果:1.6月龄SAMP8学习记忆能力较同龄SAMR1显著减退(潜伏期延长、跨平台象限次数减少)。2.RT-PCR结果(1)与正常对照组比较,模型组Pin1mRNA相对表达量降低(P<0.05),中药治疗组Pin1 mRNA相对表达量较模型组升高(P<0.05)。(2)与正常对照组比较,模型组HMGB1mRNA相对表达量升高(P<0.05),中药治疗组HMGB1 mRNA相对表达量较模型组下降(P<0.05),中药治疗组与正常组HMGB1 mRNA间比较差异无统计学意义(P>0.05)结论:1.SAMP8作为痴呆动物模型可靠。2.SAMP8小鼠脑内Pin1表达下调,HMGB1表达上调可能为AD发病的部分机制。3.益智健脑颗粒可能是通过上调Pin1表达,下调HMGB1的表达,从而起到了保护神经元、减少淀粉样斑块及神经元纤维缠结形成等作用,实现其对AD的治疗。亦提示该药具有多靶点治疗AD的作用。更多还原

【Abstract】 Objective:Through researching the effection of yizhi jiannao granule concentration fluid(YCF)on the expression of peptidy 1-prolyl -cis- trans isomerase A(Pin1)mRNA and high mobility group box 1(HMGB1)mRNA in the hippocampus of Senescence Accelerated Mouse SAMP8,this work discusses partially the mechanism of traditional Chinese medicine YCF with respect to its effectiveness to treat Alzheimer’s disease.Methods:Six--month old SAMP8 mice were randomly divided into the YCF group and model group after the Morris water maze pre-screen testing.Six--month old SAMR1 mice were served as a normal control group,the YCF group was gavaged YCF,the model group and normal control group were gavaged double-distilled water for 8 weeks, the hippocampus were taken out to examine the expression of Pin1、HMGB1 mRNA by semi-quantitative RT-PCR.Results:1.The SAMP8 mice had significantly decreased in ability o f learning and memory than the SAMR1 mice(the longer escape latency、the more times in platform quadrant)2.In the model group,the level of Pinl mRNA decreased Compared with the normal control group(P＜0.05),in the YCF group the level of Pinl mRNA increased Compared with the model group(P＜0.05).In the model group,the level of HMGB1 mRNA increased Compared with the normal control group(P＜0.05),in the YCF group the level of HMGB1 mRNA decreased Compared with the model group(P＜0.05);while the YCF group and normal control group had no significant difference.Conclusion:1.SAMP8 is reliable as a animal model of Alzheimer’s.2.The decreased level of Pin1 mRNA and the increased level of HMGB1 mRNA in the SAMP8 mice,which probably is part of pathology of Alzheimer’s disease.3.Yizhi jiannao granule can protect neurons,reduce amyloid plaques and nerve fibers tangles through increacing the Pin1 level and decreacing the HMGB1 level to treat Alzheimer’s disease.That showing Yizhi jiannao granule has multitarget mechanism of AD.更多还原