中华行为医学与脑科学杂志
中華行為醫學與腦科學雜誌
중화행위의학여뇌과학잡지
CHINESE JOURNAL OF BEHAVIORAL MEDICINE AND BRAIN SCIENCE
2012年
10期
865-868
,共4页
漆黄素%阿尔茨海默病%淀粉样蛋白%核因子E2相关因子2
漆黃素%阿爾茨海默病%澱粉樣蛋白%覈因子E2相關因子2
칠황소%아이자해묵병%정분양단백%핵인자E2상관인자2
Fisetin%Alzheimer's disease%β-amyloid%Nuclear factor(erythroid-derived 2)-like 2
目的 研究黄酮类化合物漆黄素对Aβ诱发小鼠学习功能障碍的影响.方法 通过侧脑室植入的引导管灌注Aβ (1-42)建立AD小鼠模型.Aβ灌注7d前开始每天进行漆黄素干预并持续至实验结束.Aβ灌注3d后,利用经典的水迷宫观察小鼠学习记忆功能的变化,实验结束后立即分离海马组织,提取核蛋白和总蛋白,分别利用Western blotting和RT-PCR方法检测小鼠海马核内核因子E2相关因子2(Nrf2)蛋白水平及其下游靶基因血红素加氧酶(HO-1)和γ-谷氨酰半胱氨酸连接酶(γ-GCL)催化亚基(GCLC)和修饰亚基(GCLM)的mRNA表达水平.结果 (1)水迷宫实验结果显示,漆黄素干预组[10mg/kg:( 17.54±3.56)s；20 mg/kg:( 13.04±2.36)s]较Aβ (1-42)模型组[(25.40±3.33)s；(1.70±0.05)次]能够剂量依赖性明显降低潜伏期,并增加穿过平台所在位置的次数[ 10 mg/kg:(2.50±0.40)次；20mg/kg:( 3.50±0.36)次],差异具有统计学意义(P＜0.05或P＜0.01)；(2) Western blotting和RT-PCR结果显示,漆黄素干预组较Aβ(1-42)模型组能够明显增加海马核内Nrf2蛋白表达水平(10 mg/kg:0.11±0.01;20 mg/kg:0.16±0.02),上调HO-1 (10 mg/kg:0.56±0.06;20 mg/kg:0.79±0.10)、GCLC( 10 mg/kg:0.61±0.04;20 mg/kg:0.86±0.09)和GCLM( 10 mg/kg:0.35±0.04;20 mg/kg:0.51±0.04) mRNA水平,差异均具有统计学意义(P＜0.05或P＜0.01).结论 漆黄素可有效缓解Aβ(1-42)诱发的小鼠认知功能障碍,其促智作用很可能与激活内源Nrf2抗氧化中枢信号通路有关.
目的 研究黃酮類化閤物漆黃素對Aβ誘髮小鼠學習功能障礙的影響.方法 通過側腦室植入的引導管灌註Aβ (1-42)建立AD小鼠模型.Aβ灌註7d前開始每天進行漆黃素榦預併持續至實驗結束.Aβ灌註3d後,利用經典的水迷宮觀察小鼠學習記憶功能的變化,實驗結束後立即分離海馬組織,提取覈蛋白和總蛋白,分彆利用Western blotting和RT-PCR方法檢測小鼠海馬覈內覈因子E2相關因子2(Nrf2)蛋白水平及其下遊靶基因血紅素加氧酶(HO-1)和γ-穀氨酰半胱氨痠連接酶(γ-GCL)催化亞基(GCLC)和脩飾亞基(GCLM)的mRNA錶達水平.結果 (1)水迷宮實驗結果顯示,漆黃素榦預組[10mg/kg:( 17.54±3.56)s；20 mg/kg:( 13.04±2.36)s]較Aβ (1-42)模型組[(25.40±3.33)s；(1.70±0.05)次]能夠劑量依賴性明顯降低潛伏期,併增加穿過平檯所在位置的次數[ 10 mg/kg:(2.50±0.40)次；20mg/kg:( 3.50±0.36)次],差異具有統計學意義(P＜0.05或P＜0.01)；(2) Western blotting和RT-PCR結果顯示,漆黃素榦預組較Aβ(1-42)模型組能夠明顯增加海馬覈內Nrf2蛋白錶達水平(10 mg/kg:0.11±0.01;20 mg/kg:0.16±0.02),上調HO-1 (10 mg/kg:0.56±0.06;20 mg/kg:0.79±0.10)、GCLC( 10 mg/kg:0.61±0.04;20 mg/kg:0.86±0.09)和GCLM( 10 mg/kg:0.35±0.04;20 mg/kg:0.51±0.04) mRNA水平,差異均具有統計學意義(P＜0.05或P＜0.01).結論 漆黃素可有效緩解Aβ(1-42)誘髮的小鼠認知功能障礙,其促智作用很可能與激活內源Nrf2抗氧化中樞信號通路有關.
목적 연구황동류화합물칠황소대Aβ유발소서학습공능장애적영향.방법 통과측뇌실식입적인도관관주Aβ (1-42)건립AD소서모형.Aβ관주7d전개시매천진행칠황소간예병지속지실험결속.Aβ관주3d후,이용경전적수미궁관찰소서학습기억공능적변화,실험결속후립즉분리해마조직,제취핵단백화총단백,분별이용Western blotting화RT-PCR방법검측소서해마핵내핵인자E2상관인자2(Nrf2)단백수평급기하유파기인혈홍소가양매(HO-1)화γ-곡안선반광안산련접매(γ-GCL)최화아기(GCLC)화수식아기(GCLM)적mRNA표체수평.결과 (1)수미궁실험결과현시,칠황소간예조[10mg/kg:( 17.54±3.56)s；20 mg/kg:( 13.04±2.36)s]교Aβ (1-42)모형조[(25.40±3.33)s；(1.70±0.05)차]능구제량의뢰성명현강저잠복기,병증가천과평태소재위치적차수[ 10 mg/kg:(2.50±0.40)차；20mg/kg:( 3.50±0.36)차],차이구유통계학의의(P＜0.05혹P＜0.01)；(2) Western blotting화RT-PCR결과현시,칠황소간예조교Aβ(1-42)모형조능구명현증가해마핵내Nrf2단백표체수평(10 mg/kg:0.11±0.01;20 mg/kg:0.16±0.02),상조HO-1 (10 mg/kg:0.56±0.06;20 mg/kg:0.79±0.10)、GCLC( 10 mg/kg:0.61±0.04;20 mg/kg:0.86±0.09)화GCLM( 10 mg/kg:0.35±0.04;20 mg/kg:0.51±0.04) mRNA수평,차이균구유통계학의의(P＜0.05혹P＜0.01).결론 칠황소가유효완해Aβ(1-42)유발적소서인지공능장애,기촉지작용흔가능여격활내원Nrf2항양화중추신호통로유관.
Objective To explore the effects of fisetin on the learning and memory abilities impairments induced by Aβ in mice.Methods Alzheimer's disease (AD) animal model was made by single intracerebroventricular infusion of Aβ (1-42) through guide cannula.Fisetin was orally administered 7 days before Aβ infusion once a day,and continued throughout the experimental period.Water maze test began on day 3 after Aβ infusion.All mice were sacrificed and hippocampi were dissected immediately after behavioral test.The protein expression of hippocampal nuclear Nrf2 and the mRNA level of HO-1,GCLC and GCLM were examined by western blotting and RT-RCR techniques respectively.Results ( 1 ) Aβ (1-42) significantly increased escape latency in hidden platform test ( (25.4 ± 3.33 ) s ),and decreased the number of crossings in probe test ( 1.70 ± 0.25 ) compared with control ((9.05 ± 1.37 )s) for hidden plat form ;4.50 ± 0.41 for probe test) and Aβ (42-1)-treated group ( ( 10.80 ± 1.38)s) for hidden platform test; 4.10 ±0.39 for probe test; P＜0.01 ).The prolonged treatment with fisetin dose-dependently reversed the changes (10 mg/kg:17.54 ± 3.56s for hidden platform test;2.50 ± 0.40 for probe test,P＜0.05,20 mg/kg:( 13.04 ± 2.36) s for hidden platform test;3.60 ±0.36 for probe test,P＜0.01 ).(2) Aβ (1-42) significantly decreased the nuclear Nrf2 protein level (0.07 ±0.02),and mRNA level (0.45 ±0.04) of HO-1,GCLC (0.41 ± 0.04) and GCLM (0.26 ± 0.03 ) in the hippocampus of mice compared with control (0.18 ± 0.02 for Nrf2 ;0.83 ± 0.09 for HO-1 ; 1.01 ± 0.10 for GCLC; 0.65 ± 0.07 for GCLM) and Aβ (42-1 ) -treated group (0.21 ± 0.02 for Nrf2 ; 0.90 ± 0.08 for HO-1 ; 1.11 ± 0.11 for GCLC ; 0.72 ± 0.07 for GCLM) ( P ＜ 0.05 or P ＜ 0.01 ).However,fisetin administration significantly counteracted these changes ( 10 mg/kg:0.11± 0.01 for Nrf2 ; 0.56 ± 0.06 for HO-1 ; 0.61 ± 0.04 for GCLC ; 0.35 ± 0.04 for GCLM ; 20 mg/kg:0.16 ± 0.02for Nrf2;0.79±0.10 for HO-1;0.86±0.09 for GCLC;0.51±0.04 for GCLM;P＜0.05).Conclusion Fisetin attenuates learning and memory impairments induced by Aβ (1-42) through activation of Nrf2 antioxidant signaling pathway.
