石菖蒲挥发油联合人参总皂苷通过调节PI3K/Akt/mTOR通路对痴呆模型APP/PS1双转基因小鼠的Aβ_(40)和GFAP的影响

Effects of the co-administration of total ginsenoside and volatile oil of Acorus tatarinowii Schott on the levels of Aβ_(40) and GFAP in APP/PS1 double transgenic mice by adjusting the PI3K/Akt/mTOR pathway

目的:研究石菖蒲挥发油联合人参总皂苷对APP/PS1双转基因小鼠的Aβ_(40)和GFAP的含量变化及对调节PI3K/Akt/mTOR通路的影响。方法:112只APP/PS1双转基因小鼠随机分为8组,模型组、人参总皂苷75 mg/kg组、石菖蒲挥发油15 mg/kg组、石菖蒲挥发油15 mg/kg+人参总皂苷75 mg/kg、石菖蒲挥发油30 mg/kg+人参总皂苷150 mg/kg、石菖蒲挥发油60 mg/kg+人参总皂苷300 mg/kg、雷帕霉素0. 5 mg/kg组和LY294002 0. 75 mg/kg组。正常组和模型组灌胃等体积的生理盐水,各组连续给药30 d。末次给药后采用免疫组化检测GFAP; ELISA检测Aβ_(40)和GFAP; Western blot检测p-mTOR和p-Akt。结果:与正常组比较,模型组的Aβ_(40)和GFAP表达显著增加,p-mTOR和p-Akt表达显著减少。与模型组比较,人参总皂苷组、石菖蒲挥发油组和联合各剂量组的的Aβ_(40)和GFAP表达都显著减少,雷帕霉素组的p-mTOR表达显著减少及p-Akt的表达显著增加,LY294002组的p-mTOR表达显著增加及p-Akt的表达显著减少,联合各剂量组的p-mTOR和p-Akt的表达显著增加。与人参总皂苷组和石菖蒲挥发油组比较,其中联合各剂量组的Aβ_(40)和GFAP表达都显著减少。与LY294002组比较,雷帕霉素组和联合各剂量组的p-mTOR表达显著减少及p-Akt的表达显著增加。与雷帕霉素组比较,联合各剂量组的p-mTOR表达显著增加及p-Akt的表达显著减少。结论:石菖蒲挥发油联合人参总皂苷通过上调PI3K/Akt/mTOR通路来减少APP/PS1双转基因小鼠中Aβ_(40)和GFAP表达。

Objective： To observe the effects of the co-administration of total ginsenoside and volatile oil of Acorus tatarinowii Schott on the levels of Aβ40 and GFAP in APP/PS1 double transgenic mice by adjusting the PI3 K/Akt/mTOR pathway. Methods： 112 APP/PS1 double transgenic mice were randomly divided into model group,total ginsenoside group（75 mg/kg）,volatile oil of Acorus tatarinowii Schott group（15 mg/kg）,Rapamine group（0. 5 mg/kg）,LY294002 group（0. 75 mg/kg） and co-administration of total ginsenoside and volatile oil of Acorus tatarinowii Schott group（co-administered group,the doses of volatile oil of Acorus tatarinowii Schott and total ginsenoside were 15 mg/kg and 75 mg/kg,30 mg/kg and 150 mg/kg,60 mg/kg and 300 mg/kg respectively）. Mice in the treated groups were administration with the corresponding drug form the 30 th day. Senile plaque on GFAP expression was observed by immunohistochemistry. Aβ 40 and GFAP were detected by ELISA. The expression of p-mTOR and p-Akt were detected by western blot. Results： As compared with the normal group,the expression of Aβ40 and GFAP were significantly increased（P 〈 0. 01）,but p-mTOR and p-Akt expression were significantly reduced in model group（P〈 0. 01）. As compared with the model group,the expression of Aβ40 and GFAP were significantly decreased in total ginsenoside group,volatile oil of Acorus tatarinowii Schott group and co-administered group（P 〈 0. 05）; p-mTOR expression was significantly decreased,but p-Akt expression was significantly increased in Rapamine group（P 〈 0. 05）; p-mTOR expression was significantly increased,but p-Akt expression was significantly decreased in LY294002 group（P 〈 0. 01）; p-mTOR and p-Akt expression were significantly increased in co-administered group（P 〈 0. 05）. As compared with the total ginsenoside group and volatile oil of Acorus tatarinowii Schott group,the expression of Aβ40 and GFAP were significantly decreased in co-administered group（P 〈 0. 05）. As compared with the LY294002 group,p-mTOR expression was significantly decreased,but p-Akt expression was significantly increased in Rapamine group and co-administered group（P 〈 0. 05）. As compared with the Rapamine group,p-mTOR expression was significantly increased,but p-Akt expression was significantly decreased in coadministered group（P 〈 0. 05）. Conclusion： Total ginsenoside and volatile oil of Acorus tatarinowii Schott co-administration has an effect on lessening the levels of Aβ40 and GFAP by upgrading the PI3 K/Akt/mTOR pathway.