北京中医药大学学报2024，Vol.47Issue(3)：352-363,12.DOI:10.3969/j.issn.1006-2157.2024.03.010
山茱萸醇提物调节LSD1/PSD95对Aβ25-35诱导的阿尔茨海默病小鼠神经损伤保护作用的研究
Neuroprotective effect of ethanol extract of Corni Fructus on Aβ25-35- induced Alzheimer's disease mice by regulating LSD1/PSD95
摘要
Abstract
Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.关键词
山茱萸/组蛋白特异性去甲基化酶1/组蛋白修饰/阿尔茨海默病/神经损伤/小鼠Key words
Corni Fructus/lysine-specific demethylase 1/histone modification/Alzheimer's disease/injury of nerve/mice分类
医药卫生引用本文复制引用
杨计歌,李立新,李中华,苏运芳,张紫娟,宋军营,曾华辉,张振强,马金莲..山茱萸醇提物调节LSD1/PSD95对Aβ25-35诱导的阿尔茨海默病小鼠神经损伤保护作用的研究[J].北京中医药大学学报,2024,47(3):352-363,12.基金项目
国家自然科学基金面上项目(No.82274612) （No.82274612）
河南省博士后科研项目启动基金(No.HN2022100) （No.HN2022100）
河南省高校科技创新团队支持计划(No.21IRTSTHN026)National Natural Science Foundation of China(No.82274612) （No.21IRTSTHN026）
