破壁灵芝孢子粉调控NLRP3炎症体介导的焦亡对阿尔茨海默病大鼠学习记忆能力的影响
Effects of sporoderm-broken spores of Ganoderma lucidum modulating NLRP3 inflammasome-mediated pyroptosis on learning memory ability in Alzheimer's disease rats
黄薇 1叶树 2丁志贤 1覃云鹏 1胡冠华 2李思钰 1蔡标3
作者信息
- 1. 安徽中医药大学药学院,合肥 230012
- 2. 安徽中医药大学中西医结合学院,合肥 230012
- 3. 安徽中医药大学药学院,合肥 230012;安徽中医药大学中西医结合学院,合肥 230012;中西医结合防治神经退行性疾病医药基础研究创新中心,合肥 230012
- 折叠
摘要
目的:探究破壁灵芝孢子粉(BSG)对阿尔茨海默病(AD)大鼠神经保护的作用及其机制.方法:腹腔注射D-半乳糖联合脑内注射Aβ25-25建立AD模型.40只SPF级SD大鼠随机分为假手术组(Sham组)、模型组(Model组)、破壁灵芝孢子粉组(BSG组)、多奈哌齐组(DP组),每组10只.用药组连续灌胃给药28 d.新事物实验检测大鼠学习记忆能力;HE、电镜检测海马组织损伤情况;Western blot及RT-PCR分别检测相关蛋白及mRNA的表达.结果:与Model组比较,BSG组和DP组大鼠新事物实验RI值显著升高(P＜0.05);海马神经元损伤显著减少(P＜0.05);p-tau蛋白表达水平显著降低(P＜0.05),NLRP3、ASC、Caspase-1、GSDMD、GSDMD-N蛋白和mRNA的表达水平显著降低(P＜0.05).结论:破壁灵芝孢子粉可能通过调控NLRP3炎症体的激活介导的细胞焦亡,降低相关炎症因子的表达,抑制tau蛋白过度磷酸化,发挥神经保护作用的.
Abstract
Objective:To investigate the neuroprotective effect of sporoderm-broken spores of Ganoderma lucidum(BSG)on Alzheimer's disease(AD)rats and its mechanism.Methods:Intraperitoneal injection of D-galactose combined with intracerebral injection of Aβ25-25 to establish an AD model.Forty SPF-grade SD rats were randomly divided into Sham group,Model group,sporoderm-broken spores of Ganoderma lucidum(BSG group),and Donepezil group(DP group),10 rats in each group,and the medicated group was administered with the drug by consecutive gavage for 28 days.The learning and memory ability of rats were observed by the novel object recognition test;the hippocampal tissue damage were observed by HE and electron microscopy;the expression of related proteins and respective mRNA were detected by Western blot and RT-PCR.Results:Compared with the Model group,the PI values of rats in the BSG and DP groups were increased significantly(P＜0.05);the hippocampal neuronal damage was decreased significantly(P＜0.05);the expression levels of p-tau protein were significantly reduced(P＜0.05),and the expression levels of NLRP3,ASC,Caspase-1,GSDMD,GSDMD-N proteins and mRNA were significantly reduced(P＜0.05).Conclusion:Sporoderm-broken spores of Ganoderma lucidum may play a neuroprotective role by regulating cellular pyroptosis mediated by the activation of NLRP3 inflammasome,decreasing the expression of related inflammatory factors,and inhibiting the hyperphosphorylation of tau protein.
关键词
破壁灵芝孢子粉/阿尔茨海默病/NLRP3炎症体/p-tau/神经保护/新事物识别实验/学习记忆Key words
Sporoderm-broken spores of Ganoderma lucidum/Alzheimer's disease/NLRP3 inflammasome/p-tau/Neuroprotective role/Novel object recognition test/Learning and memory引用本文复制引用
基金项目
国家自然科学基金青年科学基金(82205235)
高校学科(专业)拔尖人才学术资助项目(gxhjZD2022024)
安徽中医药大学人才支持项目(2022rcyb028)
出版年
2024
国家科技期刊平台
NSTL
万方数据