中医药导报2025，Vol.31Issue(7)：25-31,7.DOI:10.13862/j.cn43-1446/r.2025.07.004
滋肾醒脑汤通过TLR4/NF-κB/NLRP3抑制APP/PS1小鼠小胶质细胞焦亡改善认知功能研究
Zishen Xingnao Decoction(滋肾醒脑汤)Improves Cognitive Function by Inhibiting Microglial Pyroptosis in APP/PS1 Mice through TLR4/NF-κB/NLRP3 Signaling Pathway
摘要
Abstract
Objective:To investigate the effects of Zishen Xingnao decoction(ZSXND)on microglial pyroptosis and cognitive function in APP/PS1 mice.Method:Totally 50 APP/PS1 mice were randomly divided into model group,ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group,10 mice in each group,and 10 C57BL/6J mice were selected as the normal group.Drugs were administered via gavage.Learning and memory abilities were assessed using the Morris water maze test.Hematoxylin-eosin(HE)staining was used to observe neuronal morphology and Nissl staining was employed to evaluate neuronal damage.Transmission electron microscopy(TEM)was used to observe microglial ultrastructure.Immunohistochemistry was used to analyze Aβ1～42 deposition in the hippocampus and cortex.Western blotting quantified hippocampal protein levels of toll-like receptor 4(TLR4),nuclear factor κB(NF-κB),NOD-like receptor protein3(NLRP3)and Caspase-1.Results:Model group,ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group showed longer escape latency than normal group(P＜0.01 or P＜0.05).ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group exhibited shorter escape latency than model group(P＜0.05).The model group showed reduced platform quadrant retention time than normal group(P＜0.05)and model group showed fewer platform crossings than normal group(P＜0.05).ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group showed longer platform retention time than model group(P＜0.05 or P＜0.01).ZSXND medium-dose group and donepezil group showed increased platform crossings than model group(P＜0.01).HE staining showed that the neurons in the CA1 region of the hippocampus were arranged neatly and had normal morphology in normal group.There were disorganized and damaged neurons in the hippocampal CA1 region of the model group,whereas ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group showed improved neuronal structure,count,and morphology,with only minimal nuclear vacuolization and occasional heterochromatin.Nissl staining showed that Nissl bodies were evenly distributed in neurons in normal group,with regular cell morphology and tight arrangement.There were significantly reduced Nissl bodies,sparse arrangement,and cellular swelling in model group neurons.These damages were markedly ameliorated in ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group.Immunohistochemical staining showed regular morphology of neurons in the hippocampal CA1 and cortical regions in normal group.There were prominent brownish Aβ1～42 deposits surrounding neurons with abnormal morphology in model group.Aβ1～42 deposition and neuronal damage were significantly reduced in ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group.According to TEM,the morphology and structure of hippocampal microglia were normal in normal group.There were degenerated neurons and numerous vacuolated pyroptotic bodies in model group,while ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group showed improved cell shrinkage and relatively intact cell membranes.Model group showed higher TLR4,NF-κB,NLRP3,and Caspase-1 expression in hippocampal than normal group(P＜0.01).ZSXND low-dose group,ZSXND medium-dose group,ZSXND high-dose group,and donepezil group showed lower TLR4,NF-κB,NLRP3,and Caspase-1 expression in hippocampal than model group(P＜0.01).Conclusion:Zishen Xingnao decoction may exert neuroprotective effects and improve cognitive function by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway,reducing the expression of TLR4,NF-κB,NLRP3,and Caspase-1,inhibiting microglial pyroptosis,and mitigating Aβ1～42 deposition.关键词
阿尔茨海默病/滋肾醒脑汤/TLR4/NF-κB/NLRP3通路/小胶质细胞/细胞焦亡/认知功能/小鼠Key words
Alzheimer disease/Zishen Xingnao decoction/TLR4/NF-κB/NLRP3 signaling pathway/microglia/cell pyroptosis/cognitive function/mouse分类
医药卫生引用本文复制引用
邱华安,胡国恒,李宇翔,曾阳,谢丹,王焱,盛望..滋肾醒脑汤通过TLR4/NF-κB/NLRP3抑制APP/PS1小鼠小胶质细胞焦亡改善认知功能研究[J].中医药导报,2025,31(7):25-31,7.基金项目
2021年度长沙市自然科学基金项目(kq2202456) （kq2202456）
