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清心开窍方通过PI3K/Akt通路改善APP/PS1双转基因小鼠的认知能力、抑制细胞凋亡并减少病理沉积物。

Qingxin Kaiqiao Recipe Improves Cognitive Performance, Inhibits Apoptosis, and Reduces Pathological Deposits in APP/PS1 Double Transgenic Mice via the PI3K/Akt Pathway.

作者信息

Lin Shi-Yi, Wang Tian-Qi, Xu Lu-Ting, Lai Xiao-Xiao, Shen Yan, Lin Jian-Wei, Gao Shi-Yu, Hu Hai-Yan

机构信息

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Lu Cheng District, Wenzhou 325000, China.

The Second Clinical College, Wenzhou Medical University, Wenzhou 325003, China.

出版信息

Evid Based Complement Alternat Med. 2020 Apr 28;2020:3019674. doi: 10.1155/2020/3019674. eCollection 2020.

DOI:10.1155/2020/3019674
PMID:32419798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7204341/
Abstract

The traditional Chinese medicine of Qingxin Kaiqiao Recipe (QKR) is effective in the treatment of Alzheimer's disease (AD). This study aims to investigate whether QKR improves the cognitive ability and takes neuroprotective effect on APP/PS1 double transgenic mice via the PI3K/Akt pathway. APP/PS1 double transgenic mice were randomly divided into a model, donepezil-treated, or QKR-treated group (L-QKR: 4.75 mg/kg/d, M-QKR: 9.5 mg/kg/d, and H-QKR: 19 mg/kg/d, respectively). Wild-type C57/BL6J mice were used as the control group. Morris water maze (MWM) was used to test the ability of spatial navigation and memorization; terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay was applied to test the apoptosis; amyloid protein granule deposition was detected via Methenamine silver staining; Western blot (WB) analysis, immunohistochemistry, and RT-PCR were applied to measure the expression of A and corresponding indicators of the PI3K/Akt pathway. Compared with the model group, QKR significantly relieved the cognitive impairment, reduced the deposition of senile plaques, decreased the expression of GSK-3 and A, and increased the expression of p-PI3K, p-Akt, and IDE. In addition, the number of TUNEL-positive cells decreased after treatment using QKR. The current study proved that QKR, especially at the high dose tested, exerted a protective effect on improving learning and memory, inhibiting apoptosis, and reducing the process of pathological degeneration in the hippocampus of AD mice.

摘要

清心开窍方(QKR)这一传统中药在治疗阿尔茨海默病(AD)方面具有疗效。本研究旨在探究QKR是否能改善认知能力,并通过PI3K/Akt信号通路对APP/PS1双转基因小鼠发挥神经保护作用。将APP/PS1双转基因小鼠随机分为模型组、多奈哌齐治疗组或QKR治疗组(低剂量QKR组:4.75mg/kg/d,中剂量QKR组:9.5mg/kg/d,高剂量QKR组:19mg/kg/d)。野生型C57/BL6J小鼠作为对照组。采用莫里斯水迷宫(MWM)测试空间导航和记忆能力;应用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)检测法检测细胞凋亡;通过六胺银染色检测淀粉样蛋白颗粒沉积;采用蛋白质免疫印迹(WB)分析、免疫组织化学和逆转录聚合酶链反应(RT-PCR)检测A的表达以及PI3K/Akt信号通路的相应指标。与模型组相比,QKR显著缓解了认知障碍,减少了老年斑沉积,降低了GSK-3和A的表达,并增加了p-PI3K、p-Akt和IDE的表达。此外,QKR治疗后TUNEL阳性细胞数量减少。当前研究证明,QKR,尤其是在本研究测试的高剂量下,对改善AD小鼠海马体的学习和记忆、抑制细胞凋亡以及减少病理退变过程具有保护作用。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ed/7204341/2ef7c8036476/ECAM2020-3019674.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ed/7204341/f9aa56aa894e/ECAM2020-3019674.002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ed/7204341/c6d8fe10403e/ECAM2020-3019674.007.jpg

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