中国实验方剂学杂志2026，Vol.32Issue(17)：77-86,10.DOI:10.13422/j.cnki.syfjx.20260804
安寐丹调控SIRT3/Nrf2信号通路介导线粒体氧化改善老年睡眠剥夺模型小鼠认知功能的机制
Anmei Dan Regulates SIRT3/Nrf2 Signaling Pathway-mediated Mitochondrial Oxidative Stress to Improve Cognitive Function in Aged Sleep-deprived Mouse Model
摘要
Abstract
Objective:To investigate the mechanism by which Anmei Dan(AMD)regulates recombinant sirtuin 3/nuclear factor erythroid 2-related factor 2(SIRT3/Nrf2)signaling to ameliorate mitochondrial oxidative stress and improve the cognitive function in aged sleep-deprived mice.Methods:Sixty aged C57 mice were randomly assigned to a control group,a model group,a melatonin(1.3 mg·kg-1·d-1)group,and high-,medium-,and low-dose(26.26,13.13,6.565 g·kg-1·d-1,respectively)AMD groups,with ten mice per group.Continuous sleep deprivation was administered for 4 weeks via a custom-built sleep deprivation chamber.The cognitive function of mice was assessed via the Morris water maze test.Hematoxylin-eosin(HE)staining was performed to observe morphological alterations in pyramidal neurons.Biochemical assays were carried out to measure the hippocampal and serum levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),catalase(CAT),and total antioxidant capacity(T-AOC).Transmission electron microscopy was adopted to examine mitochondrial pathological alterations in the hippocampus.Immunohistochemical assay was conducted to examine the expression of nuclear factor E2-related factor 2(Nrf2),sirtuin 3(SIRT3),peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α),mitochondrial transcription factor A(TFAM),and brain-derived neurotrophic factor(BDNF)in the mouse hippocampus.The protein levels of Nrf2,SIRT3,heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1)in mouse hippocampal tissue were determined by Western blot.Immunofluorescence double labeling was employed to determine the protein levels of SIRT3/Nrf2 in mouse hippocampal tissue.Results:Compared with the control group,the model group exhibited prolonged latency to navigate,increased total swimming distance,reduced number of platform crossings,and shortened time spent in the target quadrant(P<0.05,P<0.01),disorganized morphology and arrangement of hippocampal neurons,with increased damaged mitochondria,mitochondrial swelling,reduced cristae,and vacuolization,declined levels of SOD,GSH-Px,CAT,and T-AOC and elevated levels of MDA in the hippocampus and serum(P<0.01),and downregulated protein levels of SIRT3,Nrf2,PGC-1α,TFAM,BDNF,HO-1,and NQO1(P<0.01).Compared with the model group,the melatonin group and AMD groups exhibited shortened spatial navigation latency,reduced total swimming distance,increased number of platform crossings,and prolonged activity time in the target quadrant(P<0.05,P<0.01),reduced neuronal damage and mitochondrial damage in the hippocampal tissue,declined level of MDA and elevated levels of SOD,GSH-Px,CAT,and T-AOC in the hippocampus and serum(P<0.05,P<0.01),and upregulated protein levels of SIRT3,Nrf2,PGC-1α,TFAM,BDNF,HO-1,and NQO1 in the hippocampus(P<0.05,P<0.01).Conclusion:AMD may improve the learning and memory in aged sleep-deprived mice by mediating mitochondrial oxidative damage through the SIRT3/Nrf2 signaling pathway.关键词
安寐丹/老年睡眠剥夺/认知功能/线粒体氧化损伤/沉默信息调节因子3(SIRT3)/核因子E2相关因子2(Nrf2)信号通路Key words
Anmei Dan/aged sleep deprivation/cognitive function/mitochondrial oxidative stress/recombinant sirtuin 3/nuclear factor erythroid 2-related factor 2(SIRT3/Nrf2)signaling pathway分类
医药卫生引用本文复制引用
王力春,马金旭,王子傲,王平,谢光璟..安寐丹调控SIRT3/Nrf2信号通路介导线粒体氧化改善老年睡眠剥夺模型小鼠认知功能的机制[J].中国实验方剂学杂志,2026,32(17):77-86,10.基金项目
国家自然科学基金项目(82305354) （82305354）
湖北省自然科学基金创新发展联合基金项目(2026AFC0897) （2026AFC0897）
