中药药理与临床2025，Vol.41Issue(11)：39-44,6.
丹龙醒脑方通过Nrf2/Keap1信号通路影响血管性痴呆大鼠突触可塑性的研究
Danlong Xingnao(丹龙醒脑)Formula Regulates Synaptic Plasticity in Rat Model of Vascular Dementia via Nrf2/Keap1 Signaling Pathway
摘要
Abstract
Objective:To study the mechanism of Danlong Xingnao(丹龙醒脑)Formula on the prevention and treatment of vascular dementia in rats.Methods:Ten rats were randomly selected from 60 rats as the sham operation group,and the other rats were subjected to modified bilat-eral common carotid artery occlusion for the modeling of vascular dementia.The modeled rats were randomized into model,Danlong Xingnao Formula(3.7,7.4,and 14.8 g/kg),and positive control(nimodipine,0.01 g/kg)groups.After 28 days of administration,Morris water maze test was carried out to examine the escape latency and platform crossings.The synaptic ultrastructure in the hippocampal tissue was ob-served by transmission electron microscopy.The expression of growth-associated protein 43(GAP43)in the hippocampal tissue was detected by immunohistochemistry.The activities of superoxide dismutase(SOD)and glutathione(GSH)and the content of malondiadehyde(MDA)in the liver tissue of mice were detected by the biochemical method.The mRNA and protein levels of nuclear factor-erythroid 2-related factor 2(Nrf2),Kelch-like ECH-associated protein 1(Keap1),heme oxygenase-1(Ho-1),synapsin(Syp),postsynaptic dense protein-95(Psd-95),GAP43,brain-derived neurotrophic factor(Bdnf),and N-methyl-D-aspartate receptor subunit 2B(Nr2b)in the hippocampal tissue were determined by real-time PCR and Western blotting,respectively.Results:Compared with the sham operation group,the model group showed increased escape latency,MDA content,and mRNA and protein levels of Keap1(P<0.01),pathological changes in the synaptic ultrastructure of the hippocampal tissue,reduced platform crossings(P<0.01),decreased SOD and GSH activities(P<0.01),inhibited expression of GAP43 in the hippocampus(P<0.01),and down-regulated mRNA and protein levels of Nrf2,Ho-1,Syp,Psd-95,Gap43,Bdnf,and Nr2b in the hippocampus(P<0.01).Compared with the model group,Danlong Xingnao Formula significantly reduced the escape latency and in-creased the platform crossings of rats(P<0.05,P<0.01),reduced synaptic ultrastructural damage in the hippocampus,increased the expres-sion of GAP43 in the hippocampus(P<0.05 or P<0.01),enhanced the SOD and GSH activities,reduced the MDA content(P<0.05 or P<0.01),up-regulated the mRNA and protein levels of Nrf2,Ho-1,Syp,Psd-95,Gap43,Bdnf,and Nr2b(P<0.05 or P<0.01),and down-regu-lated the mRNA and protein levels of Keap1 in the hippocampus(P<0.05,P<0.01).Conclusion:Danlong Xingnao(丹龙醒脑)Formula is beneficial for improving synaptic plasticity and learning and memory abilities in the rat model of vascular dementia.It may exert the therapeu-tic effect by activating the Nrf2/Keap1 signaling pathway,alleviating oxidative stress,repairing pathological damage of the synaptic ultrastruc-ture in the hippocampal tissue,and up-regulating the expression of synaptic proteins.关键词
丹龙醒脑方/血管性痴呆/核因子-红细胞2相关因子2/Kelch样ECH关联蛋白1信号通路/突触可塑性/氧化应激Key words
Danlong Xingnao(丹龙醒脑)Formula/Vascular dementia/Nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap 1)signaling pathway/Synaptic plasticity/Oxidative stress引用本文复制引用
杨梦琳,张运辉,周小青,伍大华,刘霞,杨昆,程妍..丹龙醒脑方通过Nrf2/Keap1信号通路影响血管性痴呆大鼠突触可塑性的研究[J].中药药理与临床,2025,41(11):39-44,6.基金项目
国家自然科学基金项目(编号:81874462) （编号:81874462）
重庆市教委科学技术研究计划项目(编号:KJQN202302708) （编号:KJQN202302708）
重庆市中医药传承创新团队-三峡库区道地药材保护与利用多学科交叉创新团队(编与:CXTD202303) （编与:CXTD202303）
万州区博士直通车项目(编号:wzst20230415). （编号:wzst20230415）
