Résumé
OBJECTIVE@#To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics.@*METHODS@#Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis.@*RESULTS@#Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway.@*CONCLUSION@#Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.
Sujets)
Femelle , Rats , Animaux , Glucocorticoïdes/effets indésirables , AMP-Activated Protein Kinases , Protéomique , Rat Sprague-Dawley , Ostéoporose/génétique , Protéines nucléaires/effets indésirablesRésumé
Zexietang is a Chinese herbal compound prescription with a long history, which consists of Rhizoma alismatis and Atractylodes macrocephala. Zexietang comes from "Synopsis of Golden Chamber", as "there is a drink under the heart, and its people are bitter and dizzy". Zexietang has the effect of removing water from drinking water and invigorating spleen for diuresis. Modern pharmacological studies have shown that its lipid-lowering and anti-inflammatory effects are very significant. It can be used to treat hyperlipidemia, anti-atherosclerosis and non-alcoholic fatty liver disease. With the continuous development of molecular biology, the research on the pharmacological effects of Zexietang, extracts and their monomers has deepened to the molecular level gradually, and the relevant mechanism of action has also been continuously elucidated. In terms of lipid-lowering effect of Zexietang, the levels of cytokines or receptors such as 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), and liver X receptors (LXR) are affected. It is widely involved in adenosine 5'-monophosphate-activated protein kinase (AMPK) and peroxisome proliferators-activated receptors (PPAR) pathways, while Zexietang's anti-inflammatory effect mainly affects inflammatory factors such as interleukins (IL) and tumor necrosis factors (TNF), and simultaneously nuclear factor κB (NF-κB), toll-like receptors (TLR) and other cytokines or receptor-related pathways. In order to promote the further research and clinical application of Zexietang and contribute to the development of modernization of traditional Chinese medicine, the studies of the past 15 years on molecular mechanism of the lipid-lowering and anti-inflammatory effect of Zexietang, Alisma and Atractylodes extract as well as their monomer components were reviewed.