三七总皂苷对快速老化痴呆模型小鼠SAMP8脑内氧化应激相关信号通路的影响研究

项目名称： 三七总皂苷对快速老化痴呆模型小鼠SAMP8脑内氧化应激相关信号通路的影响研究

项目编号： No.81460598

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 钟振国

作者单位： 广西中医药大学

项目金额： 48万元

中文摘要： 三七总皂苷（PNS）对老年性痴呆(AD)有防治作用，能抑制β淀粉样蛋白（β-AP）表达和显著降低氧化应激水平。前期研究证实,PNS通过调节β-AP代谢通路中的一些转录因子和酶的活性而抑制β-AP的形成，但PNS影响氧化应激信号网络具体部位仍不清楚。本项目以快速老化痴呆模型小鼠SAMP8为研究对象，采用酶活性检测试剂盒、免疫组化、Western blot和定量PCR等方法，观察PNS对与氧化应激信号网络中相关通路的SOD、GPx、CAT、GSH、UCP4、UCP5、PI3K、PKC、JAK、MAPK、JNK、Akt、PLCγ-1、Nrf2、ARE、STAT、p38、p53蛋白及酶的影响，阐明PNS影响氧化应激信号网络具体环节，明确其作用靶点，进一步阐明PNS治疗AD的分子机制，为开发PNS防治AD提供更多的科学依椐。广西是三七的主要产地，资源丰富，它的开发利用将促进我区经济和社会的发展。

中文关键词： 三七总皂苷；老年性痴呆；快速老化痴呆模型小鼠SAMP8；氧化应激；信号通路

英文摘要： Panax Notoginseng Saponins (PNS) shows pronounced control effects on Alzheimer's Disease (AD), inhibiting the expression of beta amyloid protein (β-AP), and prominently decreasing oxidative stress level in the AD model of rat. Our previous study demonstrated that PNS inhibited the β-AP formation through regulating activities of some transcription factors and enzymes in β-AP metabolic pathway. However, it is still unknown the specific signalling pathways involving PNS anti-oxidative effects. Current study is designed to investigate the effects of PNS on proteins and enzymes involved in the oxidative stress signaling pathways in the brain of senescence accelerated mouse-prone 8 (SAMP8), particularly focused on SOD, GPx, CAT, GSH, UCP4, UCP5, PI3K, PKC, JAK,MAPK, JNK, Akt, PLCγ-1, Nrf2, ARE, STAT,p38 and p53 by using methods of immunohistochemistry, western blote, PCR, and specific enzyme activity assay kits. It is expectative to illuminate the molecular mechanisms underlined in the protective effects of PNS on AD. The research will provide the theoretical basis for developing PNS as a promising AD drugs. The exploitation and utilization of PNS can also promote the development of economy and society in Guangxi province.

英文关键词： Panax Notoginseng Saponins;Alzhermer's disease;senescence accelerated mouse-prone 8;oxidative stress;signaling pathways