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电针改善阿尔茨海默病大鼠模型的认知缺陷并激活过氧化物酶体增殖物激活受体γ

Electroacupuncture improves cognitive deficits and activates PPAR-γ in a rat model of Alzheimer's disease.

作者信息

Zhang Min, Xv Gui-Hua, Wang Wei-Xin, Meng Di-Juan, Ji Yan

机构信息

Nursing College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.

Medical College of Jiangsu University, Zhenjiang, Jiangsu Province, China.

出版信息

Acupunct Med. 2017 Mar;35(1):44-51. doi: 10.1136/acupmed-2015-010972. Epub 2016 Jul 11.

Abstract

BACKGROUND

Alzheimer's disease (AD) is an age-associated neurodegenerative disorder that is associated with a progressive impairment of cognition. Acupuncture has protective effects, although the molecular mechanisms are largely unknown. The activation of peroxisome proliferator activated receptor γ (PPAR-γ) has an impact on the pathogenesis of AD.

OBJECTIVE

To test the hypothesis that electroacupuncture (EA) confers therapeutic benefits through activation of PPAR-γ in a rat model of AD.

METHODS

80 male Sprague-Dawley rats were randomly divided into four groups (n=20 each): Control (healthy control group), Sham (sham-operated group), AD (untreated AD model group), and AD+EA (AD model group treated with EA). The AD model was induced in the latter two groups by injection of amyloid-β (Aβ)1-40 into the hippocampal CA1 area bilaterally. EA was administered at GV20 and BL23 six times per week for 4 weeks. The rats' behaviour was examined using the Morris water maze test, and protein expression of Aβ, hyperphosphorylated tau protein (p-Tau), PPAR-γ, and hyperphosphorylated p38 mitogen activated protein kinase (p38MAPK) in the hippocampal CA1 region was examined by immunohistochemistry and Western blotting.

RESULTS

EA significantly improved cognitive deficits and reduced Aβ and p-Tau Ser404 protein concentrations in the hippocampal CA1 region. AD decreased PPAR-γ and increased p-p38MAPK, while EA significantly upregulated PPAR-γ expression and significantly downregulated p-p38MAPK expression.

CONCLUSIONS

Acupuncture at GV20 and BL23 might have a beneficial effect on rats with AD via activation of PPAR-γ and inhibition of p-p38MAPK expression.

摘要

背景

阿尔茨海默病(AD)是一种与年龄相关的神经退行性疾病,与认知功能的进行性损害有关。针刺具有保护作用,但其分子机制大多未知。过氧化物酶体增殖物激活受体γ(PPAR-γ)的激活对AD的发病机制有影响。

目的

验证电针(EA)通过激活AD大鼠模型中的PPAR-γ发挥治疗作用的假说。

方法

将80只雄性Sprague-Dawley大鼠随机分为四组(每组n = 20):对照组(健康对照组)、假手术组(假手术操作组)、AD组(未治疗的AD模型组)和AD+EA组(接受EA治疗的AD模型组)。后两组通过双侧海马CA1区注射淀粉样β蛋白(Aβ)1-40诱导建立AD模型。每周在GV20和BL23穴位进行6次EA治疗,共4周。采用Morris水迷宫试验检测大鼠行为,并通过免疫组织化学和蛋白质印迹法检测海马CA1区Aβ、磷酸化tau蛋白(p-Tau)、PPAR-γ和磷酸化p38丝裂原活化蛋白激酶(p38MAPK)的蛋白表达。

结果

EA显著改善了认知缺陷,并降低了海马CA1区Aβ和p-Tau Ser404蛋白浓度。AD导致PPAR-γ降低和p-p38MAPK升高,而EA显著上调PPAR-γ表达并显著下调p-p38MAPK表达。

结论

针刺GV20和BL23穴位可能通过激活PPAR-γ和抑制p-p38MAPK表达对AD大鼠产生有益作用。

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