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二肽基肽酶-4抑制剂改善糖尿病大鼠的认知功能。

DPP-4 Inhibitor Improved the Cognitive Function in Diabetic Rats.

作者信息

Hu Ying, Wang Jiancheng, Wang Jiao, Chen Wen, Zhang Qin

机构信息

Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.

Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi 330006, China.

出版信息

J Healthc Eng. 2022 Nov 18;2022:8280389. doi: 10.1155/2022/8280389. eCollection 2022.

DOI:10.1155/2022/8280389
PMID:39280108
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11401724/
Abstract

Diabetes-associated cognitive dysfunction is a major problem of the international community. Dipeptidyl peptidase-4 (DPP-4) inhibitors are drugs with hypoglycemic effect widely used in diabetic treatment in clinic. In this article, we studied the effect of the DPP-4 inhibitor saxagliptin on cognitive function in diabetic rats. Firstly, to observe cognitive dysfunction caused by diabetes, we built the diabetic rat model. Subsequently, the effect of diabetes on cognitive function was evaluated by Morris Water Maze Task. Thirdly, the mechanism of the alleviation effect of DPP-4 inhibitor on cognitive dysfunction was investigated. Specifically, (1) the anti-inflammation mechanism was revealed by quantifying the accumulation of the inflammatory factor interleukin-1 (IL-1) in the hippocampus area by western blotting and the glial fibrillary acidic protein (GFAP) by immunohistochemistry; (2) the anti-tau phosphorylation mechanism was revealed by quantifying phosphorylated tau by western blotting. This work represents the first study demonstrating the alleviation effect of DPP-4 inhibitor on cognitive dysfunction caused by diabetes. Results obtained here could be useful to seeking for a medical solution with high efficacy to the diabetes-associated cognitive dysfunction.

摘要

糖尿病相关认知功能障碍是国际社会面临的一个重大问题。二肽基肽酶-4（DPP-4）抑制剂是临床上广泛用于糖尿病治疗的具有降血糖作用的药物。在本文中，我们研究了DPP-4抑制剂沙格列汀对糖尿病大鼠认知功能的影响。首先，为了观察糖尿病引起的认知功能障碍，我们构建了糖尿病大鼠模型。随后，通过莫里斯水迷宫任务评估糖尿病对认知功能的影响。第三，研究了DPP-4抑制剂对认知功能障碍的缓解作用机制。具体而言，（1）通过蛋白质印迹法对海马区炎症因子白细胞介素-1（IL-1）的积累进行定量，并通过免疫组织化学法对胶质纤维酸性蛋白（GFAP）进行定量，揭示抗炎机制；（2）通过蛋白质印迹法对磷酸化tau进行定量，揭示抗tau蛋白磷酸化机制。这项工作是第一项证明DPP-4抑制剂对糖尿病引起的认知功能障碍具有缓解作用的研究。此处获得的结果可能有助于寻找一种对糖尿病相关认知功能障碍具有高效的医学解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/15b745a26cad/JHE2022-8280389.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/7dbe0b54b715/JHE2022-8280389.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/9768495cb0e6/JHE2022-8280389.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/8d41506a236c/JHE2022-8280389.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/eac0235b6201/JHE2022-8280389.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/15b745a26cad/JHE2022-8280389.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/7dbe0b54b715/JHE2022-8280389.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/9768495cb0e6/JHE2022-8280389.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/8d41506a236c/JHE2022-8280389.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/eac0235b6201/JHE2022-8280389.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9148/11401724/15b745a26cad/JHE2022-8280389.005.jpg

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Antidiabetic Drugs in Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review.抗糖尿病药物在阿尔茨海默病和轻度认知障碍中的应用：系统评价。
Dement Geriatr Cogn Disord. 2020;49(5):423-434. doi: 10.1159/000510677. Epub 2020 Oct 20.
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Vascular cognitive impairment and dementia in type 2 diabetes mellitus: An overview.2 型糖尿病患者的血管性认知功能障碍和痴呆：概述。
Life Sci. 2020 Aug 1;254:117771. doi: 10.1016/j.lfs.2020.117771. Epub 2020 May 11.
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Novel repair mechanisms in a renal ischaemia/reperfusion model: Subsequent saxagliptin treatment modulates the pro-angiogenic GLP-1/cAMP/VEGF, ANP/eNOS/NO, SDF-1α/CXCR4, and Kim-1/STAT3/HIF-1α/VEGF/eNOS pathways.
在肾缺血/再灌注模型中发现的新的修复机制：后续的沙格列汀治疗可调节促血管生成的 GLP-1/cAMP/VEGF、ANP/eNOS/NO、SDF-1α/CXCR4 和 Kim-1/STAT3/HIF-1α/VEGF/eNOS 通路。
Eur J Pharmacol. 2019 Oct 15;861:172620. doi: 10.1016/j.ejphar.2019.172620. Epub 2019 Aug 19.
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Diabetes mellitus and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 144 prospective studies.糖尿病与认知障碍和痴呆风险：144 项前瞻性研究的系统评价和荟萃分析。
Ageing Res Rev. 2019 Nov;55:100944. doi: 10.1016/j.arr.2019.100944. Epub 2019 Aug 17.
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The Growing Epidemic of Diabetes Mellitus.糖尿病的流行日益加剧。
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