Effects of Ziziphi Spinosae Semen and Albiziae Flos on Behavior and Endoplasmic Reticulum Stress PERK/ATF4/CHOP Pathway in Depression Model Rats
10.13422/j.cnki.syfjx.20210205
- VernacularTitle:酸枣仁-合欢花对抑郁模型大鼠行为学及内质网应激PERK/ATF4/CHOP通路的影响
- Author:
Zhi-yi CAO
1
;
Ling LI
1
;
Li-li FAN
1
;
Ming-jie WANG
2
;
Chao-feng GUO
1
;
Xue-li SHI
1
Author Information
1. Guangxi University of Chinese Medicine， Nanning 530200， China
2. The First Affiliated Hospital of Guangxi University of Chinese Medicine， Nanning 530023， China
- Publication Type:Research Article
- Keywords:
Ziziphi Spinosae Semen （ZSS） and Albiziae Flos （AF）;
depression;
protein kinase R-like endoplasmic reticulum kinase （PERK）;
CCAAT/enhancer-binding protein-homologous protein （CHOP）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(7):66-72
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of Ziziphi Spinosae Semen （ZSS） and Albiziae Flos （AF） on behavior and endoplasmic reticulum stress endoplasmic reticulum stress protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/CCAAT enhancer binding protein （CHOP） pathway in depression model rats， and to explore its antidepressant mechanism. Method:The male SD rats were divided into normal group， model group， ZSS-AF high dose， middle dose and low dose groups （16， 8， 4 g·kg-1） and Venlafaxine group （0.008 g·kg-1）， n=15 in each group. Except the normal group， the depression model was established in the rats of other 5 groups by the method of chronic unpredictable mild stress （CUMS） combined with isolated feeding. The normal group and model group were given with distilled water by gavage when modeling， while other groups received corresponding drug by intragastric administration for 21 days. Behavior changes of rats in each group were observed by the open field test and sugar water consumption test on 1th and 21thday of the experiment. The protein expressions of PERK， CHOP， B-cell lymphoma-2 associated X protein （Bax） and cysteine-containing aspartate-specific proteases-3（Caspase-3） were detected by Western blot（WB）， the ultrastructural changes of the hippocampus were observed by transmission electron microscope， the apoptosis of hippocampal neurons was observed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL） method. Result:Compared with the normal group， the scores of open field test and sugar water consumption rate in model group rats decreased （P<0.01）. Compared with the model group， the scores of open field test and water consumption rate increased （P<0.01） in ZSS-AF groups and Venlafaxine group. Transmission electron microscope showed that the changes of neuronal damage in hippocampal were revealed in the model group， whereas those neuronal damages were relieved in ZSS-AF groups and Venlafaxine group. TUNEL method showed that the number of apoptotic neurons in hippocampal increased in the model group （P<0.01）， but decreased in ZSS-AFgroups and Venlafaxine group （P<0.01）. WB results showed that as compared with the normal group， protein expressions of PERK， CHOP， Bax and Caspase-3 were up-regulated significantly in the model group （P<0.01）， whereas those were down-regulated in ZSS-AF groups and Venlafaxine group （P<0.05， P<0.01）. Conclusion:The antidepressant effect of ZSS-AF herbal pair may be correlated with the regulation of endoplasmic reticulum stress PERK/ATF4/-CHOP pathway.
