中华神经科杂志
中華神經科雜誌
중화신경과잡지
Chinese Journal of Neurology
2010年
3期
222-226
,共5页
高宝兵%龙志敏%贺桂琼%孙善全
高寶兵%龍誌敏%賀桂瓊%孫善全
고보병%룡지민%하계경%손선전
高压氧%阿尔茨海默病%衰老斑%淀粉样β蛋白%早老素1%小鼠,转基因
高壓氧%阿爾茨海默病%衰老斑%澱粉樣β蛋白%早老素1%小鼠,轉基因
고압양%아이자해묵병%쇠로반%정분양β단백%조로소1%소서,전기인
Hyperberie oxygenation%Alzheimer disease%Senile plaques%Amyloid beta-protein%Presenilin-1%Mice,transgenic
目的 探讨常压高氧(40%O_2,60%空气)处理淀粉样蛋白前体/早老素1(APP/PS1)双重转基因小鼠是否发挥神经保护作用.方法 对APP/PS1双重转基因阿尔茨海默病(AD)模型种鼠交配后产下的子代小鼠进行基因分型,待子代达10周龄时,取双重转基因小鼠40只,随机分成A、B、C、D 4组,每组10只,A、B 2组小鼠喂养于常压高氧中8 h/d,A组持续4周,B组持续8周;C、D组喂养于空气中4或8周,分别作为A、B组的对照.高氧处理后采用免疫组织化学、Thioflavin S染色检测小鼠脑组织形态学的变化,Western blot检测APP代谢过程中相关蛋白的表达变化,ELISA定量检测小鼠脑内β-淀粉样蛋白(Aβ)水平的变化.结果 免疫组织化学和Thioflavin S染色均显示,与对照组相比,高氧处理组小鼠皮质和海马内老年斑数量明显减少,B组比A组减少更显著.高氧处理组小鼠脑内C_(99)、C_(83)水平显著高于对照组,Aβ水平明显低于对照组,但各组小鼠脑内全长APP及β位淀粉样前体蛋白裂解酶1(BACE1)蛋白水平无明显改变.ELISA结果提示,B组小鼠海马和皮质内Aβ_(40)[(783.6±97.2)pg/ml]和Aβ_(42)[(175.3±17.1)ps/ml]含量明显低于对照组Aβ_(40)[(1251.6±42.3)pg/ml,t=9.36,P<0.01]和Aβ_(42)[(286.8±13.0)pg/ml,t=13.7,P<0.01]的含量.结论 常压高氧处理能显著减少AD模型小鼠脑内Aβ的产生、沉积及老年斑的形成;这种改变可能通过减少Aβ产生或加速Aβ清除实现.
目的 探討常壓高氧(40%O_2,60%空氣)處理澱粉樣蛋白前體/早老素1(APP/PS1)雙重轉基因小鼠是否髮揮神經保護作用.方法 對APP/PS1雙重轉基因阿爾茨海默病(AD)模型種鼠交配後產下的子代小鼠進行基因分型,待子代達10週齡時,取雙重轉基因小鼠40隻,隨機分成A、B、C、D 4組,每組10隻,A、B 2組小鼠餵養于常壓高氧中8 h/d,A組持續4週,B組持續8週;C、D組餵養于空氣中4或8週,分彆作為A、B組的對照.高氧處理後採用免疫組織化學、Thioflavin S染色檢測小鼠腦組織形態學的變化,Western blot檢測APP代謝過程中相關蛋白的錶達變化,ELISA定量檢測小鼠腦內β-澱粉樣蛋白(Aβ)水平的變化.結果 免疫組織化學和Thioflavin S染色均顯示,與對照組相比,高氧處理組小鼠皮質和海馬內老年斑數量明顯減少,B組比A組減少更顯著.高氧處理組小鼠腦內C_(99)、C_(83)水平顯著高于對照組,Aβ水平明顯低于對照組,但各組小鼠腦內全長APP及β位澱粉樣前體蛋白裂解酶1(BACE1)蛋白水平無明顯改變.ELISA結果提示,B組小鼠海馬和皮質內Aβ_(40)[(783.6±97.2)pg/ml]和Aβ_(42)[(175.3±17.1)ps/ml]含量明顯低于對照組Aβ_(40)[(1251.6±42.3)pg/ml,t=9.36,P<0.01]和Aβ_(42)[(286.8±13.0)pg/ml,t=13.7,P<0.01]的含量.結論 常壓高氧處理能顯著減少AD模型小鼠腦內Aβ的產生、沉積及老年斑的形成;這種改變可能通過減少Aβ產生或加速Aβ清除實現.
목적 탐토상압고양(40%O_2,60%공기)처리정분양단백전체/조로소1(APP/PS1)쌍중전기인소서시부발휘신경보호작용.방법 대APP/PS1쌍중전기인아이자해묵병(AD)모형충서교배후산하적자대소서진행기인분형,대자대체10주령시,취쌍중전기인소서40지,수궤분성A、B、C、D 4조,매조10지,A、B 2조소서위양우상압고양중8 h/d,A조지속4주,B조지속8주;C、D조위양우공기중4혹8주,분별작위A、B조적대조.고양처리후채용면역조직화학、Thioflavin S염색검측소서뇌조직형태학적변화,Western blot검측APP대사과정중상관단백적표체변화,ELISA정량검측소서뇌내β-정분양단백(Aβ)수평적변화.결과 면역조직화학화Thioflavin S염색균현시,여대조조상비,고양처리조소서피질화해마내노년반수량명현감소,B조비A조감소경현저.고양처리조소서뇌내C_(99)、C_(83)수평현저고우대조조,Aβ수평명현저우대조조,단각조소서뇌내전장APP급β위정분양전체단백렬해매1(BACE1)단백수평무명현개변.ELISA결과제시,B조소서해마화피질내Aβ_(40)[(783.6±97.2)pg/ml]화Aβ_(42)[(175.3±17.1)ps/ml]함량명현저우대조조Aβ_(40)[(1251.6±42.3)pg/ml,t=9.36,P<0.01]화Aβ_(42)[(286.8±13.0)pg/ml,t=13.7,P<0.01]적함량.결론 상압고양처리능현저감소AD모형소서뇌내Aβ적산생、침적급노년반적형성;저충개변가능통과감소Aβ산생혹가속Aβ청제실현.
Objective In order to investigate whether normobaric hyperoxia exert ncumprotective effect on amyloid protein precursor/presenilin 1(APP/PS1)double transgenic Alzheimer's disease(AD) mouse model.Methods Forty APP/PS1 double transgenie mice were randomly divided into 4 groups(A,B,C and D).Mice were treated with 40% oxygen for 8 h per day for 4 weeks in group A and for 8 weeks in group B.Group C and group D were given regular air for 4 weeks and 8 weeks,respectively,as controls.Immunohistochemical staining.Thioflavin S staining.Western blot and ELISA assay were performed on mice brain tissues in all groups after the treatment.Results Immuohistochemical and Thioflavin S staining showed that in hyperoxia-treated mice,number and size of senile plaques in the cerebral cortex and hippocampus were notably decreased,and deposition of AB in the brain of group B decreased more than that of group A.Western blot revealed that in the hyperoxia-treated mice,the levels of C_(99) and C_(83) were greatly increased while the Aβ level notably decreased.compared with controls.However,the expression of holoprotein APP and β-site amyloid cleavage enzyme 1(BACE1)showed no difference among 4 groups.ELISA assay showed that Aβ_(40)((783.6±97.2)pg/m1)and Aβ_(42)((175.3±17.1)pg/ml)were significantly decreased in the brain of 8 weeks hyperoxia-treated mice compared witlI the control group Aβ_(40) ((1251.6±42.3)pg/ml,t=9.36,P<0.01),and A1342((286.8±13.0)pg/ml,t=13.7,P<0.01).Conclusion Treatment with hyperoxia can significantly decrease Aβ levels and lower the number and size of senile plaques in the brain of APP/PS1 transgenic mouse.This study indicates that hyperoxia may exert its neuroprotective effect through decreasing the generation of Aβ or accelerating the clearance of Aβ.
