Mechanism of Yuejuwan in Prevention and Treatment of Psychological and Heart Diseases Based on Liver TMT Labeled Quantitative Proteomics
10.13422/j.cnki.syfjx.20230191
- VernacularTitle:基于肝脏TMT标记定量蛋白质组学技术研究越鞠丸防治“双心疾病”的作用机制
- Author:
Hanwen ZHANG
1
;
Jiaxiang YU
1
;
Yan SHI
1
;
Wenshun ZHANG
1
;
Xueying HAN
2
;
Huan ZHANG
1
;
Chao QU
1
;
Xinhui SHEN
1
;
Xiande MA
1
;
Rui YU
1
;
You YU
3
Author Information
1. Liaoning University of Traditional Chinese Medicine（TCM），Shenyang 110847，China
2. College of Pharmacy，Liaoning University of TCM，Dalian 116600，China
3. Second Affiliated Second Affiliated Hospital in Liaoning University of TCM，Shenyang 110034，China
- Publication Type:Journal Article
- Keywords:
Yuejuwan;
psychological and heart diseases;
prevention and treatment;
liver;
TMT labeled quantitative proteomics
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(1):26-36
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effects of Yuejuwan in the treatment of psychological and heart diseases （PHD） and explore its mechanism. MethodThirty 6-week-old healthy male SPF AopE-/- mice and 10 homologous C57BL/6J mice were selected for the experiment. The 30 AopE-/- mice were divided into a model group， low-dose （7.58 g·kg-1·d-1） and high-dose （30.32 g·kg-1·d-1） Yuejuwan groups， with 10 mice in each group， and 10 C57BL/6J mice were assigned to the blank control group. Intragastrical administration lasted 12 weeks. During feeding， the PHD model was induced by chronic unpredictable mild stress （CUMS） combined with high-fat diet in mice. After intragastric administration， the behavioral results ［open field test （OFT） and sucrose preference test （SPT）］ of mice in each group， the content of aspartic transaminase （AST）， alanine aminotransferase （ALT）， 5-hydroxytryptamine （5-HT）， noradrenaline （NE）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， total cholesterol （TC）， and triglyceride （TG） in serum of mice detected by the automatic biochemical analyzer， the oil red O staining and HE staining of aorta and liver and Masson staining of myocardial tissues were used for model evaluation. Finally， liver TMT-labeled quantitative proteomics was used to explore the mechanism of action. ResultThe model mice showed obvious manifestations of depression， anxiety， loss of interest， and despair， manifest lipid deposition in the aorta and liver by pathological observation， and increased myocardial fibrosis in myocardial tissues. After intragastric administration of Yuejuwan， the above symptoms and indexes of the PHD model mice were improved. Compared with the blank control group， the model group showed decreased standing times， cumulative time in the central area， total moving distance， moving speed， and sucrose preference at week 12 （P<0.01）. Compared with the model group， the Yuejuwan groups showed decreased indexes mentioned above （P<0.01）. After sample collection， AST， ALT， and TG levels in the model group were higher （P<0.01） and the levels of 5-HT， NE， and HDL-C were lower than those in the blank control group （P<0.01）. The results of liver TMT labeled quantitative proteomics suggested that the PHD model mainly caused the changes in protein expression levels such as ApoE， UGT1A5， and FASN in mice，involving acetyl CoA metabolism，response to bacteria，cellular amino acid catabolism， and other processes，which were related to the abnormal metabolic function of the liver. The efficacy of Yuejuwan against PHD was achieved mainly through the regulation of high mobility group nucleosomal-binding domain 2 （HMGN2）， CALD1， and Mup7 protein expression levels and correcting the biological processes and abnormal pathways related to the pathogenesis of PHD，including muscle contraction，tight junction pathway，myocardial contraction pathway，and focal adhesion pathway. ConclusionCUMS combined with high-fat diet is reasonable in the induction of the PHD model in AopE-/- mice. Yuejuwan can correct the depression and anxiety conditions of PHD model mice，reduce the aortic plaque， and recover the abnormal blood lipid and liver function levels. Furthermore， Yuejuwan can correct abnormal biological processes and pathways of PHD model mice. The differential proteins screened throughout the experiment and the involved physiological and pathological changes are the focus of the next experiment.
