Aβ25～35致阿尔茨海默病小鼠的脑海马组织炎症因子及BDNF表达分析

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中文摘要：目的探究β-淀粉样蛋白25～35(Aβ25～35)致阿尔茨海默病(AD)样小鼠脑海马炎症因子及脑源性神经营养因子(BDNF)的表达。方法取40只6周龄雄性昆明小鼠，采用双侧脑室注射Aβ25～35 构建AD样小鼠模型，分为0 d、7 d、14 d、28 d组进行观察，各10只。采用Y迷宫和新物体识别测试检测小鼠学习和记忆功能，采用苏木素-伊红(HE)染色观察海马区神经元损伤程度，采用免疫组织化学染色检测海马组织磷酸化tau(p-tau)、CD11b、BDNF的表达，采用ELISA检测海马组织炎症因子白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)表达水平，采用实时荧光定量逆转录PCR(RT-qPCR)、Western blot检测BDNF mRNA和蛋白相对表达水平。结果 Aβ25～35 可损伤小鼠记忆和认知功能。与0 d组相比，14 d、28 d组小鼠海马组织神经元数量明显减少(P<0。05)，p-Tau、CD11b光密度值和IL-1β、TNF-α表达水平明显升高(P<0。05)。此外，与0 d组相比，7 d组小鼠海马组织BDNF mRNA和蛋白相对表达水平明显升高(P<0。05)，14 d、28 d组BDNF mRNA和蛋白相对表达水平明显降低(P<0。05)。结论 Aβ25～35 可能通过活化小胶质细胞，增加海马组织TNF-α、IL-1β及p-tau的表达，进而损伤小鼠记忆和认知功能，且海马组织BDNF表达水平在损伤期先增后降。

外文标题：Analysis of inflammatory factors and BDNF expression in the brain hippocampus of Alzheimer's disease-like mice caused by Aβ25-35

外文摘要：Objective To investigate the expression of inflammatory factors and brain-derived neurotro-phic factor(BDNF)in the brain hippocampus of Alzheimer's disease(AD)-like mice caused by amyloid β-protein 25-35(Aβ25-35).Methods A total of 40 six-week-old male Kunming mice were taken to construct an AD-like mouse model using bilateral ventricular injection of Aβ25-35,and were divided into the 0 d,7 d,14 d,and 28 d groups for observation,with 10 mice in each group.The Y-maze and new object recognition assay were used to test the learning and memory functions of the mice.The hematoxylin-eosin(HE)staining was used to observe the neuronal damage in the hippocampal region.Immunohistochemical staining was used to detect the expression levels of phosphorylated-tau(p-tau),CD11b and BDNF in hippocampus.ELISA was used to detect the expression levels of inflammatory factors in hippocampus,including interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF)-α,and real-time quantitative reverse transcription PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of BDNF.Results Aβ25-35 could impair memory and cognitive function in the mice.Compared with the 0 d group,the neuron number in the hippocampal tissue of mice in the 14 d and 28 d groups was significantly reduced(P<0.05),and the optical density values of p-Tau and CD11b,and expression levels of IL-1β and TNF-α in the hippocampal region of mice in the 14 d and 28 d groups were significantly increased(P<0.05).In addition,compared with the 0 d group,the relative expression levels of BDNF mRNA and protein in the hippocampal tissue of mice were sig-nificantly increased in the 7 d group(P<0.05),while the relative expression levels of BDNF mRNA and pro-tein were significantly decreased in the 14 d and 28 d groups(P<0.05).Conclusion Aβ25-35 may increase the expression of TNF-α,IL-1β and p-tau in hippocampal tissue by activating microglia,which in turn impaired the memory and cognitive functions of mice,and the expression level of BDNF in hippocampal tissue showed a first increase and then a decrease in the injury period.

外文关键词：

Alzheimer's diseasehippocampal tissueinflammatory factorsbrain-derived neurotrophic factoramyloid β-protein

作者：

陆雯、任锦烨、何湘伟、唐亮、李建明

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作者单位：

长沙医学院临床学院长沙 410219

长沙医学院神经变性病基础与临床湖南省高校重点实验室,长沙 410219

关键词：

阿尔茨海默病海马组织炎症因子脑源性神经营养因子 β-淀粉样蛋白

基金：

湖南省教育厅重点项目湖南省教育厅重点项目湖南省长沙市杰出创新青年人才计划项目湖南省大学生创新项目湖南省双一流应用特色学科湖南省普通高等学校科技创新团队支持计划项目

项目编号：

22A066223A0661kq2206058湘教通[2019]219号-2393湘教通[2022]351号湘教通[2023]233号

出版年：

2024

DOI：

10.3969/j.issn.1671-8348.2024.05.004

重庆医学

重庆市卫生信息中心,重庆市医学会

重庆医学

CSTPCD

影响因子：1.797

ISSN：1671-8348

年,卷(期)：2024.53(5)

参考文献量36