Effect of Dingzhi Xiaowan on PI3K/Akt/mTOR/HIF-1α Pathway in Post-stroke Cognitive Impairment Model Mice
10.13422/j.cnki.syfjx.20241804
- VernacularTitle:定志小丸对卒中后认知障碍模型小鼠PI3K/Akt/mTOR/HIF-1α通路的影响
- Author:
Han ZHANG
1
;
Yu WANG
1
;
Xiaoqin ZHONG
2
;
Zhenqiu NING
1
;
Dafeng HU
1
;
Minzhen DENG
1
Author Information
1. State Key Laboratory of Traditional Chinese Medicine Syndrome（TCM），The Second Affiliated Hospital of Guangzhou University of Chinese Medicine/Guangdong Provincial Hospital of Chinese Medicine/ Guangdong Branch of Chinese Academy of Chinese Medical Sciences，Guangzhou 510120，China
2. Shenzhen Bao'an TCM Hospital/Bao'an TCM Hospital Affiliated to Guangzhou University of Chinese Medicine，Shenzhen 518100，China
- Publication Type:Journal Article
- Keywords:
Dingzhi Xiaowan;
dementia;
phosphoinositol-3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor 1-alpha （HIF-1α） pathway;
ischemic stroke;
ischemia-reperfusion
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(5):1-11
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of Dingzhi Xiaowan （DZXW） in post-stroke cognitive impairment （PSCI） model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group， model group， low-dose DZXW group （1.43 g·kg-1）， and high-dose DZXW group （2.56 g·kg-1）， with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage， and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein （APP）， amyloid 42 （Aβ42）， acetylcholinesterase （AChE）， and superoxide dismutase （SOD） were measured by enzyme-linked immunosorbent assay （ELISA）. Deoxyribonucleotide end transferase-mediated nick end labelling （TUNEL） assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor 1-alpha （HIF-1α）， B-cell lymphoma 2 （Bcl-2） homologous structural domain protein （Beclin1）， sequestosome 1 （p62）， microtubule-associated protein light chain 3 （LC3）， Bcl-2， and Bcl-2-associated X protein （Bax） in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group， the latency， APP， Aβ42， AChE， TUNEL positivity， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly increased in the model group （P<0.01）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly decreased （P<0.01）. Compared with the model group， the latency， APP， Aβ42， AChE， TUNEL positivity rate， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups （P<0.05）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly higher （P<0.05）. ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.
