Effect of Danggui Shaoyaosan on Mitochondrial Homeostasis and AMPK/SIRT1/PGC-1α Signaling Pathway in Rats Model of Alzheimer's Disease
10.13422/j.cnki.syfjx.20222343
- VernacularTitle:当归芍药散对AD大鼠线粒体稳态及AMPK/SIRT1/PGC-1α信号通路的影响
- Author:
Miao YANG
1
;
Wenjing YU
1
;
Chunxiang HE
1
;
Yijie JIN
1
;
Ze LI
1
;
Ping LI
1
;
Sisi DENG
1
;
Yaqiao YI
1
;
Shaowu CHENG
1
;
Zhenyan SONG
1
Author Information
1. Hunan Province Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine， Hunan University of Chinese Medicine， Changsha 410208， China
- Publication Type:Journal Article
- Keywords:
Danggui Shaoyaosan;
Alzheimer's disease;
mitochondrial homeostasis;
adenosine 5'-monophosphate （AMP）-activated protein kinase（AMPK）;
recombinant sirtuin 1（SIRT1）;
peroxisome proliferators-activated receptor γ coactivator l alpha（PGC-1α）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(3):9-16
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of Danggui Shaoyaosan （DSS） on the morphology and function of mitochondria in rats model of Alzheimer's disease （AD） and its possible mechanism. MethodRats model of AD was established by injection of streptozocin （STZ） into bilateral ventricles of SD rats. The 40 rats were randomly divided into sham group， model group， low， medium and high dosages of Danggui Shaoyaosan （12，24，36 g·kg-1·d-1） groups，observed the morphological changes of mitochondria in hippocampus of rats by electron microscopy after 14 days of continuous gavage. In situ end labeling（TUNEL） staining used to detect apoptosis and immunofluorescencereactive used to observe the expression of reactive oxygen species （ROS） and peroxisome proliferators-activated receptor γ coactivator lalpha （PGC-1α），quantitative Real-time polymerase chain reaction（Real-time PCR）detected the mRNA expression of dynamin-related protein 1 （Drp1），mitochondrial fusion protein 2 （MFN2） ，cytochrome C oxidase subunit Ⅳ （COX Ⅳ） and PGC-1α. Western blot detected the protein expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK），phosphorylation（p）-AMPK，recombinant Sirtuin 1 （SIRT1） and PGC-1α. ResultCompared with the sham group，the results of model group showed that the damage of mitochondria in hippocampus was more obvious，accelerated the ROS production and apoptosis rate （P<0.01），decreased the mRNA level of MFN2，COX Ⅳ，PGC-1α，increased the mRNA level of Drp1，and descended the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.05，P<0.01）.Compared with the model group，the medium and high dose of DSS group notably improved the damage of mitochondria，reduced the production of ROS and apoptosis rate （P<0.01），promoted the mRNA expression of MFN2，COX Ⅳ，PGC-1α，inhibited the mRNA expression of Drp1，and up-regulated the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.01）. ResultDSS can significantly ameliorate the mitochondrial homeostasis imbalance in AD rats.
