针刺研究

2014, v.39(04) 272-277

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电针对APP转基因鼠神经元自噬途径的影响
Effect of Electroacupuncture Intervention on Autophagy Pathway in APP 695V717I Transgenic Mice

薛卫国;张忠;许红;葛桂玲;白丽敏;
XUE Wei-guo;ZHANG Zhong;XU Hong;GE Gui-ling;BAI Li-min;School of Acu-moxibustion and TuinaBeijing University of Chinese Medicine;School of Basic Medicine,Beijing University of Chinese Medicine;Scientific Research Centre,Beijing University of Chinese Medicine;

摘要(Abstract):

目的:从神经元自噬途径的角度,探讨电针治疗阿尔茨海默病的可能作用机制。方法:将12只13月龄APP转基因雌性小鼠随机分为模型组和电针组,以相同月龄和背景的C 57BL/6小鼠6只做对照组。电针组取"百会""涌泉"穴,疏密波,频率2Hz/100Hz,强度1~2mA,每次留针15min,隔日1次,治疗3个月。每组6只动物取半脑做纹状皮层常规Aβ1-42免疫组化、TUNEL染色,取另半脑做纹状皮层透射电镜观察。结果:免疫组化结果显示,Aβ1-42主要表达于皮层锥体神经元,与对照组相比,模型组Aβ1-42细胞内表达增强(P<0.01);透射电镜结果显示,模型组皮层神经元胞体及突起有大量自噬体;TUNEL染色显示,与对照组相比,模型组皮层凋亡细胞数目增多(P<0.01)。而电针组Aβ1-42细胞内表达减弱(P<0.01),神经细胞自噬体明显减少,凋亡细胞数目减少(P<0.05)。结论:APP 695V717I转基因鼠存在神经元自噬途径功能紊乱及神经元内Aβ1-42水平增高;对神经元自噬途径功能的调节,可能是电针改善阿尔茨海默病的作用机制之一。
Objective To observe the effect of electroacupuncture(EA)therapy on the intraneuronal Aβ1-42 and dysfunction of autophagy pathway,so as to reveal its mechanism underlying improvement of Alzheimer's disease(AD).MethodsAPP 695V717 Itransgenic female mice were randomly divided into model group(n=6)and EA group(n=6);and C 57BL/6mice were used as the control group(n=6).After 3months' treatment by EA therapy at"Baihui"(GV 20)and"Yongquan"(KI 1)(15min,once every other day,2Hz/100 Hz,1-2mA),the expression level of Aβ1-42 of the striate cortex was detected by immunohistochemistry.TUNEL staining was used to detect the degree of apoptosis of the striate cortex,and ultrastructural changes of autophagosome in the cortex were observed using electron microscope.Results In comparison with the control group,Aβ1-42 expression level and the apoptotic neurons in the striate cortex were significantly up-regulated in the model group(P<0.01).Following EA intervention for 3months,the Aβ1-42 expression level and the number of apoptotic neurons were significantly decreased in the EA group(P<0.01,P<0.05).Accordingly,transgenic induced dark degenerated neurons exhibiting irregular body deformation,analosis,and abundant secondary lysosomes and autophagosomes were reduced in the EA group.Conclusion EA intervention can effectively down-regulate Aβ1-42 expression and number of the apoptotic neurons in the striate cortex in APP transgenic model mice,which may contribute to its effect in improving pathological changes of ultrastructure of neurons.

关键词(KeyWords): 阿尔茨海默病;APP转基因鼠;电针干预;自噬途径
Alzheimer's disease;APP transgenic mice;Electroacupuncture intervention;Autophagy pathway

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(No.81273826)

作者(Author): 薛卫国;张忠;许红;葛桂玲;白丽敏;
XUE Wei-guo;ZHANG Zhong;XU Hong;GE Gui-ling;BAI Li-min;School of Acu-moxibustion and TuinaBeijing University of Chinese Medicine;School of Basic Medicine,Beijing University of Chinese Medicine;Scientific Research Centre,Beijing University of Chinese Medicine;

Email:

DOI: 10.13702/j.1000-0607.2014.04.003

参考文献(References):

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