黑逍遥散对阿尔茨海默病模型小鼠Ca2+-CaM/CaMKⅡα信号通路关键因子表达的影响  

Effects of Heixiaoyao Powder on Expression of Key Factors of Ca2+-CaM/CaMKⅡα Signaling Pathway of AD Model Mice

作　　者：马春林[1] 吴红彦 兰美华 程坚 段永强[1] MA Chunlin;WU Hongyan;LAN Meihua;CHENG Jian;DUAN Yongqiang(Gansu University of Chinese Medicine,Lanzhou 730000,China;Shenzhen Luohu People’s Hospital,Shenzhen 518020,China;Shenzhen Luohu Hospital of TCM,Shenzhen 518001,China)

机构地区：[1]甘肃中医药大学,甘肃兰州730000 [2]深圳市罗湖区人民医院,广东深圳518020 [3]深圳市罗湖区中医院,广东深圳518001

出　　处：《中国中医药信息杂志》2019年第10期50-54,共5页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金地区基金(81660760);兰州市人才创新创业扶持项目(2015-RC-24)

摘　　要：目的观察黑逍遥散对阿尔茨海默病(AD)小鼠海马神经元Ca^2+浓度和钙调蛋白(CaM)、钙调蛋白依赖性激酶Ⅱα(CaMKⅡα)表达的影响。方法30只APP/PS1双转基因雄性小鼠称重后,按随机原则分为模型组、阳性对照组和黑逍遥散组,每组10只。另取10只同月龄、同种系野生型C57BL/6雄性小鼠为空白组。各给药组给予相应药物干预,连续3个月,采用钙荧光探针结合激光共聚焦显微镜技术检测海马神经元Ca^2+浓度,采用实时荧光定量PCR和免疫组化技术分别检测小鼠海马区CaM、CaMKⅡα基因和蛋白的表达。结果与空白组比较,模型组小鼠海马神经元Ca^2+浓度显著升高,CaM基因和蛋白表达显著升高,CaMKⅡα基因和蛋白表达显著降低(P<0.01,P<0.05);与模型组比较,各给药组小鼠海马神经元Ca^2+浓度显著降低,CaM基因和蛋白表达显著降低,CaMKⅡα基因和蛋白表达显著升高(P<0.01,P<0.05)。结论黑逍遥散通过调节模型小鼠海马Ca^2+-CaM/CaMKⅡα信号通路关键因子表达而发挥防治AD的作用。Objective To observe the effects of Heixiaoyao Powder on the concentration of Ca^2+and expressions of calmodulin,CaMKⅡααgenes or proteins in the hippocampus neurons of Alzheimer disease(AD)mice.Methods After weighing,30 APP/PSI genetically modified mice were randomly divided into model group,positive medicine control group,and Heixiaoyao Powder groups,with 10 mice in each group.Ten wild-type C57BL/6 male mice of the same age and same species were set as blank group.Each administration group was given relevant medicine.After three-month successive gavage,calcium fluorescence probe combined with laser confocal microscopy was used to detect the Ca^2+concentration in hippocampal neurons,and real-time quantitative PCR and immunohistochemistry were used to detect the expressions of CaM and CaMKⅡαgenes and proteins in hippocampus of mice.Results Compared with the blank group,the Ca^2+concentration in the hippocampal neurons of the model group significantly increased,and the expressions of CaM gene and protein were significantly increased,while the expressions of CaMKⅡαgene and protein were decreased(P<0.01,P<0.05).Compared with the model group,the concentration of Ca^2+in hippocampal neurons of mice significantly decreased.The expressions of CaM gene and protein were significantly decreased,while the expressions of CaMKⅡαgene and protein were significantly increased(P<0.01,P<0.05).Conclusion Heixiaoyao Powder can prevent and treat AD by regulating the concentration of Ca^2+-CaM/CaMKⅡαsignal pathway in the hippocampus of model mice.

关 键 词：黑逍遥散 阿尔茨海默病 海马组织 CA^2+浓度 钙调蛋白 钙调蛋白依赖性激酶Ⅱα 小鼠 

分 类 号：R285.5[医药卫生—中药学]