三焦针法对阿尔茨海默病模型小鼠学习和记忆功能及相关基因的影响  

Effect of Sanjiao Acupuncture on Learning and Memory Function and Related Genes in Alzheimer’s Disease Model Mice

作　　者：张雪竹[1] 刘涛[1] 贾玉洁[1] 韩景献[1] 聂坤[1] ZHANG Xuezhu;LIU Tao;JIA Yujie;HAN Jingxian;NIE Kun(First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin,300193)

机构地区：[1]天津中医药大学第一附属医院

出　　处：《中医杂志》2019年第12期1056-1061,共6页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81574049,81473766)

摘　　要：目的探讨三焦针法治疗阿尔茨海默病(AD)的可能作用机制。方法以SAMP8小鼠为AD动物模型。60只SAMP8小鼠随机分为对照组、针刺组和非穴组,每组20只。针刺组小鼠给予三焦针法干预,穴位选取“膻中”“中脘”“气海”及双侧“血海”“足三里”。非穴组取双侧肋下固定非经非穴点,左右各1个。对照组进行与以上两组相同时间、程度的捉抓刺激。每天1次。干预1个月后连续5天每天采用Morris水迷宫隐蔽平台测试检测各组小鼠学习记忆能力,再提取各组小鼠海马组织的总RNA用于基因芯片检测。基因芯片检测数据导入LINCS项目下CREEDS网络在线分析工具进行模拟效应、反向效应模式的基因差异表达模式分析。提取各组小鼠海马组织,采用等重同位素多标签相对定量蛋白质组分分析(i TRAQ)法,以对照组海马蛋白质谱为背景,寻找针刺组与非穴组差异表达蛋白,并在DAVID在线生物信息学注释工具中检索相应蛋白生物学功能。结果针刺组小鼠第1-5天逃避潜伏期均较对照组和非穴组显著缩短(P <0. 05);反向效应模式分析结果显示,针刺组反向效应相关的疾病是亨廷顿舞蹈病和胎儿酒精发育失调疾病;单基因反向效应模式分析结果显示,与针刺组基因表达模式相反度最高排名前2的基因分别是Pde10a和Pink1;单基因模拟效应模式分析显示,针刺效应在基因表达水平与Wfs1和Psap基因过表达的效应相似;小分子药物模拟效应模式分析显示,针刺组在基因表达水平与小分子药物D型丝氨酸的表达特征最相似。对i TRAQ定量分析蛋白质组的注释,发现针刺上调了神经元突起以及线粒体相关蛋白的表达。结论三焦针法可明显改善SAMP8小鼠学习记忆能力,可能是通过触发一种包含调节神经元突触可塑性、激发神经元内质网细胞应激反应和神经保护、逆转神经退行性病变进程等多个功能模块的复杂反�Objective To explore the possible mechanism of Sanjiao acupuncture in the treatment of Alzheimer's disease ( AD). Methods SAMP8 mice were selected as animal models of AD. Sixty SAMP8 mice were randomly divided into a control group,an acupuncture group and a non-acupoint group,with 20 rats in each group. The mice in the acupuncture group were given Sanjiao acupuncture method,and the acupuncture points were selected as “Danzhong ( RN17)”,“Zhongwan ( RN12)”,“Qihai ( RN6)”and bilateral “Xuehai ( SP10 )”and “Zusanli ( ST36)”. The non-acupoint group selected fixed non-acupoint under the bilateral ribs,one point in each side. The control group was subjected to the same time and degree of capture stimulation as the above 2 groups,once a day. Morris water maze concealed platform test was used to test the learning and memory ability of each group for 5 days after 1 month intervention. Total RNA from hippocampus of each group of mice was extracted for gene chip detection. The gene chip detection data was imported into the CREEDS network online analysis tool under the Library of Integrated Network-Based Cellular Signatures ( LINCS) project to analyze the gene differential expression patterns of the simulated effect and the reverse effect mode. The hippocampus tissues of each group were extracted,and the isobaric tags for relative and absolute quantitation ( iTRAQ) method was used to find the differentially expressed protein between the acupuncture group and the non-acupoint group in the background of the hippocampus protein spectrum of the control group. The corresponding protein biological function was retrieved in DAVID online bioinformatics annotation tool. Results The escape latency on the first to fifth day of the acupuncture group was significantly shorter than that of the control group and the non-acupoint group ( P < 0. 05). The reverse effect pattern analysis showed that the reverse effect related disease of the acupuncture group was Huntington' s disease and fetal alcohol development disorders;s

关 键 词：阿尔茨海默病 三焦针法 学习记忆能力 基因分析 

分 类 号：R245[医药卫生—针灸推拿学] R-332[医药卫生—中医临床基础]