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“调脏醒神”电针对 db/db 小鼠认知障碍的改善作用及其与内质网应激的关系

"Adjust Zang and arouse spirit" electroacupuncture ameliorates cognitive impairment by reducing endoplasmic reticulum stress in db/db mice.

机构信息

Institute of Acupuncture and Massage, Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun Jilin, China.

Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.

出版信息

Front Endocrinol (Lausanne). 2023 Apr 19;14:1185022. doi: 10.3389/fendo.2023.1185022. eCollection 2023.

DOI:10.3389/fendo.2023.1185022
PMID:37152933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10154981/
Abstract

INTRODUCTION

Diabetic cognitive impairment (DCI) is a chronic complication of the central nervous system (CNS) caused by diabetes that affects learning and memory capacities over time. Recently, acupuncture has been shown to improve cognitive impairment in streptozotocin-induced diabetic rats. However, the effects of electroacupuncture on DCI and its underlying mechanism have not yet been elucidated in detail.

METHODS

In this study, we used db/db mice as DCI animal models which showed low cognitive, learning and memory functions. Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. The db/db mice with cognitive impairment were randomly divided into a model group (Mod) and an electroacupuncture treatment group (Acup), while db/m mice were used as a normal control group (Con). First, the mice were subjected to behavioural tests using the Morris water maze (MWM), and body weight, blood glucose, insulin, triglycerides (TG) and total cholesterol (TC) were observed; HE, Nissl, and TUNEL staining were used to observe the morphological changes and neuronal apoptosis in the mice hippocampus; Finally, Western blot and rt-PCR were applied to detect the essential proteins and mRNA of ERS and insulin signalling pathway, as well as the expression levels of Tau and Aβ.

RESULTS

Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. Moreover, electroacupuncture attenuated diabetes-induced morphological structure change, neuronal apoptosis in the hippocampus of db/db mice. Our results revealed that electroacupuncture could regulate the expression levels of Tau and Aβ by improving hippocampal ERS levels in db/db mice, inhibiting JNK activation, attenuating IRS1 serine phosphorylation, and restoring normal transduction of the insulin signaling pathway.

DISCUSSION

In summary, ERS and insulin signaling pathway paly causal roles in DCI development. Electroacupuncture can significantly alleviate the pathogenesis of DCI, improve mice's learning and memory ability, and improve cognitive dysfunction. This study adds to our understanding of the effect of acupuncture on DCI and opens the door to further research on DCI.

摘要

简介

糖尿病认知障碍(DCI)是一种由糖尿病引起的中枢神经系统(CNS)的慢性并发症,随着时间的推移会影响学习和记忆能力。最近,研究表明针刺可以改善链脲佐菌素诱导的糖尿病大鼠的认知障碍。然而,电针对 DCI 的影响及其潜在机制尚未详细阐明。

方法

本研究以 db/db 小鼠为 DCI 动物模型,其表现出认知、学习和记忆功能低下。电针对 DCI 有明显的改善作用,表现在行为学测试中空间学习和记忆功能的改善。认知障碍的 db/db 小鼠随机分为模型组(Mod)和电针治疗组(Acup),db/m 小鼠作为正常对照组(Con)。首先,通过 Morris 水迷宫(MWM)行为学测试观察小鼠的行为变化,观察体重、血糖、胰岛素、甘油三酯(TG)和总胆固醇(TC)的变化;HE、Nissl 和 TUNEL 染色观察小鼠海马的形态变化和神经元凋亡;最后,应用 Western blot 和 rt-PCR 检测 ERS 和胰岛素信号通路的关键蛋白和 mRNA,以及 Tau 和 Aβ的表达水平。

结果

电针治疗明显改善了 DCI,表现在行为学测试中空间学习和记忆功能的改善。此外,电针治疗还能减轻糖尿病诱导的 db/db 小鼠海马形态结构改变和神经元凋亡。研究结果表明,电针对 db/db 小鼠海马 ERS 水平的改善可以调节 Tau 和 Aβ的表达水平,抑制 JNK 激活,减轻 IRS1 丝氨酸磷酸化,恢复胰岛素信号通路的正常转导。

讨论

总之,ERS 和胰岛素信号通路在 DCI 的发病机制中起因果作用。电针治疗能显著减轻 DCI 的发病机制,改善小鼠的学习记忆能力,改善认知功能障碍。本研究加深了我们对针刺治疗 DCI 的认识,为进一步研究 DCI 提供了思路。

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