橄榄油改善淀粉样前体蛋白／早老素双转基因B6C3-Tg鼠认知功能的作用及机制  

Effect of olive oil on the cognitive function of APP/PS1 mice

作　　者：王继审 竺晓鸣 龙大宏[1] 石纯[1] 

机构地区：[1]广州医科大学基础学院人体解剖学教研室,广州510182 [2]香港威尔士亲王医院,中国香港

出　　处：《神经解剖学杂志》2014年第5期535-540,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81370395,81200846);广东省自然科学基金博士启动项目和面上项目(S2012040007858,S2013010014468)

摘　　要：目的:探讨橄榄油改善淀粉样前体蛋白/早老素双转基因B6C3-Tg鼠(APP/PS1鼠)认知功能的作用及机制。方法:将16只5月龄B6C3-Tg小鼠和4只同月龄野生型小鼠分为5组:正常对照组,阳性对照组,橄榄油组,脱脂橄榄油组和β谷固醇(BS)组。正常对照组和阳性对照组小鼠用生理盐水灌胃;橄榄油组、脱脂橄榄油组和BS组小鼠则分别用橄榄油、脱脂橄榄油和BS溶液灌胃。3周后用水迷宫检测小鼠认知功能;高效液相色谱法(HPLC)检测脑组织细胞膜内BS含量;ELISA法检测脑内淀粉样前体蛋白(APP)代谢产物(sAPPα和Aβ)水平;免疫组化法检测脑内Aβ沉淀情况。结果:定位航行实验显示:与正常对照小鼠相比,阳性对照组和脱脂橄榄油组小鼠的逃避潜伏期显著延长(P<0.01);而橄榄油组和BS组小鼠的逃避潜伏期与正常对照小鼠无明显差异。空间探索实验显示:阳性对照组和脱脂橄榄油组小鼠在目标象限的游泳距离占总的游泳距离的比例低于正常对照小鼠(P<0.01);而橄榄油组和BS组小鼠在目标象限的游泳距离占总的游泳距离的比例与正常对照小鼠无明显差异。HPLC分析显示,仅在橄榄油组和BS组小鼠的脑组织细胞膜内可检测到BS。ELISA和免疫组化结果显示:与正常对照小鼠相比,阳性对照和脱脂橄榄油组小鼠脑内Aβ生成增加(P<0.01),而sAPPα含量则无明显改变。橄榄油组和BS组小鼠脑内sAPPα含量与正常对照组小鼠相比有所增加(P<0.01),但Aβ的表达较阳性对照小鼠明显减少了(P<0.01)。结论:橄榄油可改善APP/PS1鼠的认知功能,其机制可能与BS在脑内的聚集以及BS对脑组织APP代谢的调节作用有关。Objective: This study aimed to testify the effect of olive oil on the cognitive function of APP/PS1 mice.Methods: Sixteen 5-month old APP /PS1 and 4(5-month old) wide-type mice were divided into 5 groups,i. e.,normal control group,positive-control group,olive oil group,plant sterol-free olive oil group and β-sitosterol( BS) group. For normal control and positive-control group,mice were fed with normal saline solution. For olive oil,plant sterol-free olive oil and BS groups,mice were fed with olive oil,plant sterol-free olive oil and BS solutions,respectively. After 3-week treatment,the cognitive function of animals was tested by Morris Maze. BS levels in brain cell membranes were tested by HPLC. APP metabolites(Aβ and sAPPα) in mouse brain were tested by ELISA. Aβ deposit in mouse brain was ana-lyzed by immunohistology. Results: Compared with normal control group,positive-control and plant sterol-free olive oil groups showed a longer escape latency of place navigation and a lower percentage of swimming distance in the target quadrant(P < 0. 01). In contrast,escape latency of place navigation and the percentage of swimming distance in the target quadrant in olive oil and BS group were similar to those of normal control group. Analysis of BS in brain cell membranes showed that BS could only be detected in the olive oil and BS groups. Both ELISA and immunohistologic analysis showed that Aβ levels in positive-control and plant sterol-free olive oil groups were higher than that in normal control group(P <0. 01). In contrast,Aβ levels in olive oil and BS group were lower than that in positive-control group whilst sAPPα levels in olive oil and BS groups were higher than that in normal control group. Conclusion: Olive oil improves the cognitive function of APP /PS1 mice,possibly through incorporation of BS into brain cell membranes and BS modulation of APP metabolism.

关 键 词：橄榄油 APP/PSl小鼠 β谷固醇 淀粉样前体蛋白 小鼠 

分 类 号：Q510.3[生物学—生物化学]