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: To investigate the effect and mechanism of olive oil on cognitive function of amyloid precursor protein / presenilin double transgenic B6C3-Tg mice (APP / PS1 mice). Methods Sixteen five-month-old B6C3-Tg mice and four wild-type mice of the same age were divided into five groups: normal control group, positive control group, olive oil group, defatted olive oil group and β-sitosterol )group. The normal control group and the positive control group were given gavage with saline; olive oil group, defatted olive oil group and BS group mice were orally administered with olive oil, defatted olive oil and BS solution respectively. Three weeks later, the cognitive function of mice was detected by water maze; the content of BS in brain cell membrane was detected by high performance liquid chromatography (HPLC); the levels of sAPPα and Aβ in brain were detected by ELISA; Immunohistochemical detection of brain Aβ precipitation. Results: The navigation experiment showed that compared with the normal control mice, the escape latency of the mice in the positive control group and the skim olive oil group was significantly prolonged (P <0.01), while the escape latency of the mice in the olive oil group and the BS group was significantly higher than that of the normal control mice There was no significant difference in control mice. Space exploration experiments showed that the ratio of the swimming distance in the target quadrant to the total swimming distance in the positive control group and the skim olive oil group was lower than that in the normal control mice (P <0.01); while the olive oil group and the BS group mice The target quadrant’s swimming distance as a percentage of total swimming distance did not differ significantly from that of normal control mice. HPLC analysis showed that BS was detected only in the cell membrane of brain tissue of olive oil group and BS group mice. The results of ELISA and immunohistochemistry showed that compared with the normal control mice, the Aβ production in the brain of the positive control group and the skim olive oil group increased (P <0.01), while the sAPPα content did not change significantly. The content of sAPPα in the olive oil group and the BS group mice brain was increased compared with that in the normal control group (P <0.01), but the expression of Aβ was significantly decreased (P <0.01). Conclusion: Olive oil can improve the cognitive function of APP / PS1 mice. The mechanism may be related to the aggregation of BS in brain and the regulation of BS on APP metabolism in brain tissue.