Mechanism of Dihuang Yinzi in Improving Astrocyte Injury and Glycolysis in AD Mice via PI3K/Akt Pathway
10.13422/j.cnki.syfjx.20230606
- VernacularTitle:地黄饮子调节PI3K/Akt信号通路保护AD小鼠脑组织星形胶质细胞损伤及糖酵解的作用机制
- Author:
Hongni YU
1
;
Mengjie SUN
1
;
Fengli WANG
1
;
Shenghua KANG
1
;
Guanghui HAN
1
;
Dongyue LI
2
;
Weizhe ZHEN
3
;
Tao MA
1
Author Information
1. Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China
2. School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China
3. China-Japan Friendship Hospital,Beijing 100029,China
- Publication Type:Journal Article
- Keywords:
Dihuang Yinzi;
Alzheimer's disease;
astrocytes;
glycolysis;
phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）;
phosphofructokinase-1 （PFK-1）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(8):10-18
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Dihuang Yinzi in improving astrocyte injury and glycolysis in Alzheimer's disease （AD） mice via regulating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， thereby improving the cognitive function of AD mice. MethodForty male APP/PS1 transgenic mice aged four months were randomly divided into a model group and a model + Dihuang Yinzi （0.25 g·kg-1） group， with 20 mice in each group. Forty C57BL/6J mice with the same background and same age were randomly divided into a control group and a control + Dihuang Yinzi （0.25 g·kg-1） group， with 20 mice in each group. The mice in the control + Dihuang Yinzi group and the model + Dihuang Yinzi group were administered with Dihuang Yinzi by gavage， and those in the control group and the model group received an equal volume of sterilized normal saline， once a day for 150 days. Morris water maze test was performed to test the ability of navigation and space exploration of mice. The protein expression of p-PI3K， PI3K， p-Akt， Akt， phosphofructokinase-1 （PFK-1）， and aldehyde dehydrogenase 3 family member B2 （ALDH3B2） in mouse brain tissues was measured by Western blot. An immunofluorescence assay was performed to detect astrocyte morphology and the expression level of ALDH3B2. ResultAs compared with the control group， the model group showed prolonged escape latency during the 2nd to 5th days of the location-based navigation （P<0.05， P<0.01）， reduced number of times crossing the target area of the platform， shortened residence time in the target quadrant （P<0.05， P<0.01）， prolonged residence time in the opposite quadrant （P<0.05）， increased surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05， P<0.01）， and down-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）， while the above experimental indexes were not significantly different in the control + Dihuang Yinzi group. Compared with the model group， the model + Dihuang Yinzi group showed shortened escape latency of APP/PS1 mice during the 2nd to 5th days of the location-based navigation （P<0.05， P<0.01）， increased number of times crossing the platform， prolonged target quadrant residence time （P<0.05， P<0.01）， shortened residence time in the opposite quadrant （P<0.05）， reduced surface area of the cell body and total length of cell protrusions of astrocytes （P<0.05）， and up-regulated protein expression of p-PI3K， p-Akt， ALDH3B2， and PFK-1 （P<0.01）. ConclusionDihuang Yinzi can improve the learning and memory ability of AD mice by activating the PI3K/Akt signaling pathway and up-regulating the protein expression of PFK-1 and ALDH3B2 to protect against astrocyte injury in brain tissues and improve glycolysis.
