中华神经科杂志
中華神經科雜誌
중화신경과잡지
Chinese Journal of Neurology
2012年
5期
302-306
,共5页
阿尔茨海默病%海马%神经元%受体,胰岛素%胰岛素受体底物蛋白质类
阿爾茨海默病%海馬%神經元%受體,胰島素%胰島素受體底物蛋白質類
아이자해묵병%해마%신경원%수체,이도소%이도소수체저물단백질류
Alzheimer disease%Hippocampus%Neurons%Receptor,insulin%Insulin receptor substrate proteins
目的 探索β-淀粉样蛋白(Aβ)寡聚体对大鼠海马神经元胰岛素受体( InsR)、胰岛素受体底物-Ⅰ(IRS-Ⅰ)和蛋白激酶B(PKB)表达的影响,以进一步探讨阿尔茨海默病(Alzheimer's disease,AD)的发病机制.方法 按照完全随机化的原则应用随机数字表将实验大鼠分为3组(每组12只),采用立体定位仪下侧脑室注射的方法给模型(AD)组大鼠注射Aβ1-422寡聚体5μl,生理盐水(NS)组大鼠注射NS 5μl,正常手术组大鼠只穿刺无注射.1周后重复操作1次,再过1周用Y-迷宫对大鼠行行为学检测以验证造模是否成功,然后通过免疫组织化学染色的方法观察海马组织相关蛋白的表达.结果 与两对照组相比,AD组大鼠在Y-迷宫检测中出现学习和记忆障碍,表现为学习获得次数增多和记忆获得次数减少.然而,NS组和正常组大鼠行为学表现无明显差别.此外,AD组大鼠海马区神经元InsR(0.12±0.01)、IRS-Ⅰ(0.14±0.02)和PKB(0.12±0.03)的表达水平也比两个对照组低(NS组:0.40±0.02、0.39±0.06、0.38±0.03,均数差异为-0.13、-0.13、-0.17；正常手术组:0.38±0.07、0.35±0.03、0.35±0.06,均数差异为-0.15、-0.07、-0.73；均P＜0.05),表现为免疫组织化学染色平均吸光度值降低.结论 Aβ1-42寡聚体引起的大鼠学习记忆功能障碍可能是由Aβ介导的海马神经元胰岛素信号转导通路发生紊乱,从而使相关蛋白表达降低所导致.
目的 探索β-澱粉樣蛋白(Aβ)寡聚體對大鼠海馬神經元胰島素受體( InsR)、胰島素受體底物-Ⅰ(IRS-Ⅰ)和蛋白激酶B(PKB)錶達的影響,以進一步探討阿爾茨海默病(Alzheimer's disease,AD)的髮病機製.方法 按照完全隨機化的原則應用隨機數字錶將實驗大鼠分為3組(每組12隻),採用立體定位儀下側腦室註射的方法給模型(AD)組大鼠註射Aβ1-422寡聚體5μl,生理鹽水(NS)組大鼠註射NS 5μl,正常手術組大鼠隻穿刺無註射.1週後重複操作1次,再過1週用Y-迷宮對大鼠行行為學檢測以驗證造模是否成功,然後通過免疫組織化學染色的方法觀察海馬組織相關蛋白的錶達.結果 與兩對照組相比,AD組大鼠在Y-迷宮檢測中齣現學習和記憶障礙,錶現為學習穫得次數增多和記憶穫得次數減少.然而,NS組和正常組大鼠行為學錶現無明顯差彆.此外,AD組大鼠海馬區神經元InsR(0.12±0.01)、IRS-Ⅰ(0.14±0.02)和PKB(0.12±0.03)的錶達水平也比兩箇對照組低(NS組:0.40±0.02、0.39±0.06、0.38±0.03,均數差異為-0.13、-0.13、-0.17；正常手術組:0.38±0.07、0.35±0.03、0.35±0.06,均數差異為-0.15、-0.07、-0.73；均P＜0.05),錶現為免疫組織化學染色平均吸光度值降低.結論 Aβ1-42寡聚體引起的大鼠學習記憶功能障礙可能是由Aβ介導的海馬神經元胰島素信號轉導通路髮生紊亂,從而使相關蛋白錶達降低所導緻.
목적 탐색β-정분양단백(Aβ)과취체대대서해마신경원이도소수체( InsR)、이도소수체저물-Ⅰ(IRS-Ⅰ)화단백격매B(PKB)표체적영향,이진일보탐토아이자해묵병(Alzheimer's disease,AD)적발병궤제.방법 안조완전수궤화적원칙응용수궤수자표장실험대서분위3조(매조12지),채용입체정위의하측뇌실주사적방법급모형(AD)조대서주사Aβ1-422과취체5μl,생리염수(NS)조대서주사NS 5μl,정상수술조대서지천자무주사.1주후중복조작1차,재과1주용Y-미궁대대서행행위학검측이험증조모시부성공,연후통과면역조직화학염색적방법관찰해마조직상관단백적표체.결과 여량대조조상비,AD조대서재Y-미궁검측중출현학습화기억장애,표현위학습획득차수증다화기억획득차수감소.연이,NS조화정상조대서행위학표현무명현차별.차외,AD조대서해마구신경원InsR(0.12±0.01)、IRS-Ⅰ(0.14±0.02)화PKB(0.12±0.03)적표체수평야비량개대조조저(NS조:0.40±0.02、0.39±0.06、0.38±0.03,균수차이위-0.13、-0.13、-0.17；정상수술조:0.38±0.07、0.35±0.03、0.35±0.06,균수차이위-0.15、-0.07、-0.73；균P＜0.05),표현위면역조직화학염색평균흡광도치강저.결론 Aβ1-42과취체인기적대서학습기억공능장애가능시유Aβ개도적해마신경원이도소신호전도통로발생문란,종이사상관단백표체강저소도치.
Objective To investigate the effect of soluble β-amyloid protein (Aβ) oligomers on the expression levels of insulin signaling transduction cascades-associated proteins including insulin receptor ( InsR),insulin receptor substrate-Ⅰ( IRS-Ⅰ) and protein kinase B (PKB) of rat hippocampal neurons,and the pathogenesis of Alzheimer's disease (AD) in depth.Methods Soluble Aβ oligomers (5 μl) were injected into the lateral ventriculus of the AD group by a microinjector under the stereotaxic apparatus.Normal saline solution ( NS,5 μl) was injected into the NS group in the same way,and the control group received the puncture without injection. It was repeated after 1 week and the behavior of all rats was evaluated by Y-maze test after 2 weeks. Then hippocampus was removed and underwent immunohistochemical staining to detect the expression of proteins associated.Results Compared with the other groups,learning and memory ability of the Aβ-treated rats were impaired.To be specific,the times of learning were increased and the times of memory were decreased. However,there was no significant difference between the NS group and the control group.Besides,the expression levels of InsR,IRS-Ⅰ,and PKB were decreased in AD group showing that a mean optical density of staining on these proteins ( InsR:0.12 ± 0.0l ; IRS-Ⅰ:0.14 ± 0.02; PKB:0.12 ± 0.03 ) was reduced in contrast with that in the NS group and the control group.Whereas there was no significant difference between the NS group (0.40 ± 0.02,0.39 ± 0.06,0.38 ± 0.03,mean difference:- 0.13,- 0.13,- 0.17,all P ＜ 0.05 ) and the control group (0.38 ± 0.07,0.35 ± 0.03,0.35 ± 0.06,mean difference:- 0.15,- 0.07,- 0.73,all P ＜ 0.05 ).Conclusions Soluble Aβ1-42 induced learning and memory disability of the rats.The mechanism might be that Aβ can lead to disorders of the insulin signaling transduction pathway of hippocampal neurons and decrease the expression levels of the proteins in the pathway.
