Modified Shuyuwan Ameliorate Neuronal Apoptosis of APP/PS1 Mice Via Akt/GSK3β/Nrf2 Pathway
10.13422/j.cnki.syfjx.20192140
- VernacularTitle: 加减薯蓣丸通过Akt/GSK3β/Nrf2通路改善APP/PS1小鼠神经元凋亡
- Author:
Jing QIU
1
;
Zi-hu TAN
1
;
Qiong YANG
2
;
Xiao-yan WANG
1
;
Fang HUANG
1
Author Information
1. Hubei University of Chinese Medicine, Wuhan 430065, China
2. Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China
- Publication Type:Research Article
- Keywords:
Alzheimer's disease;
modified Shuyuwan;
nuclear factor erythroid-2 related factor 2;
endoplasmic reticulum stress;
apoptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(21):38-44
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the effect and mechanism of modified Shuyuwan neuroprotection in APP/PS1 model mice. Method: Selecting 20 male APP/PS1 mice of 5 months old and 10 wild type mice.The mice were divided into blank group, model group and modified Shuyuwan group(14 g·kg-1·d-1),drug delivery for 28 days, and blank group and model group were given the same amount of normal saline,APP/PS1 background primary neuron model and wild type primary neurons were divided into blank group, model group and modified Shuyuwan group,tunicamycin group, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) inhibitor group.The blank group and model group were given 10% blank serum, the modified Shuyuwan group was given 5% modified Shuyuwan-containing serum, the tunicamycin group and the PI3K/Akt inhibitor group were respectively added with 2 mg·L-1 tunicamycin and 10 μmol·L-1 LY294002 on the basis of 5% modified Shuyuwan-containing serum.The spatial learning and memory ability of mice was measured by Morris water maze,and Western blot was used to detect nuclear factor erythroid-2 related factor 2(Nrf2) protein expression in hippocampus.Western blot was used to detect the protein expression of endoplasmic reticulum stress related proteins glucose regulatory protein 78(GRP78), protein kinase-like endoplasmic reticulum kinase(PERK),phosphorylation (p-)PERK and apoptosis expression of the pathway proteins eukaryotic translation initiation factor 2α(eIF2α),p-eIF2α,enhancer binding protein homologous protein(CHOP), and cysteinyl aspartate apecific proteinase 3 (Caspase-3),p-Akt, Akt, Glycogen Synthase kinase-3β(GSK3β),Nrf2. Result: In vivo experiment,compared with blank group, the learning and memory ability of APP/PS1 mice in the model group was impaired(P<0.01), and the expression level of Nrf2 in the hippocampus was decreased(P<0.01).Compared with model group, after 4 weeks of modified Shuyuwan intervention, the learning and memory ability of APP/PS1 mice in the modified Shuyuwan group was improved, and the expression level of Nrf2 in the hippocampus was significantly increased(P<0.01). In vitro experiment,Western blot analysis showed that compared with the blank group, the expression of GRP78, p-PERK/PERK,p-eIF2α/eIF2α,CHOP, and cleaved Caspase-3 proteins was increased in the model group(P<0.01).Compared with model group, modified Shuyuwan-containing serum intervention significantly reduced the expression of GRP78, p-PERK/PERK,p-eIF2α/eIF2α,CHOP, and cleaved Caspase-3 proteins(P<0.05,P<0.01).Whereas tunicamycin inhibited the protection effect of SHhuyuwan on the endoplasmic reticulum and ERS-induced apoptosis(P<0.05). Western blot results showed that compared with blank group, the expression of p-Akt/Akt and Nrf2 protein was significantly decreased and the expression of GSK-3β was increased in the model group(P<0.01).Compared with model group, the expression of p-Akt/Akt and Nrf2 protein was significantly increased and the expression of GSK-3β was decreased after modified Shuyuwan-containing serum intervention(P<0.05,P<0.01). The effect of modified Shuyuwan on the expression of p-Akt, Nrf2 and GSK3β protein was inhibited by LY294002.(P<0.05,P<0.01). Conclusion: Modified Shuyuwan can increase Nrf2 protein expression through PI3K/Akt/GSK3β signaling pathway, reduce neuronal apoptosis induced by endoplasmic reticulum stress,improve the learning and memory ability of APP/PS1 model mice.
