Effect and metabolomic analysis of the mechanism of Buzhong Yiqi decoction on mice with high-altitude stress ulcer
[Objective]High-altitude stress ulcer(HSU)is mainly caused by the unique plateau hypoxic environment,which increases the viscosity of gastric mucosal blood,leads to anaerobic metabolism in the stomach,increases the acidity of gastric juice,and aggravates capillaries damage,eventually resulting in gastric mucosal ulcers.The clinical manifestations of HSU include epigastric pain and discomfort,fullness,pantothenic acid,epigastric burning sensation,nausea,belching,and other symptoms.In traditional Chinese medicine,HSU falls under the categories of"epigastric pain"and"stomach bloating"in traditional Chinese medicine.Buzhong Yiqi decoction,recorded in"PI WEI LUN",is an effective prescription for treating HSU,though its therapeutic mechanism remains unclear.Investigating the mechanism of HSU and developing related preventive drugs are of great significance for the health of people living at high altitudes and for foreign tourists.This study analyzes the effect of Buzhong Yiqi decoction on gastric mucosal damage in mice with HSU,and explores the mechanism by which Buzhong Yiqi decoction prevents plateau stress gastric ulcer in mice,based on metabolomics.[Methods]A hypobaric oxygen chamber was used to construct a mouse model of HSU.60 KM mice were randomly divided into five groups:model group,normal group,Buzhong Yiqi decoction low-dose group,Buzhong Yiqi decoction high-dose group,and positive drug group.The effect of Buzhong Yiqi decoction on gastric mucosal damage caused by plateau stress gastric ulcer was analyzed by comparing body mass changes,apparent morphology of gastric mucosa,and hematoxylin-eosin staining of gastric mucosa of mice in each group.Protein expression of glucose-6-phosphate dehydrogenase(G6PDH)and transcription factor YY1 was detected using Western blotting to verify whether Buzhong Yiqi decoction regulates the expression of G6PDH and YY1 proteins related to hypoxia.Metabolite analysis of mouse gastric tissue samples was performed using liquid chromatography-mass spectrometry technology,with differential metabolites statistically analyzed,and metabolic pathway enrichment analysis conducted.[Results]Pathological analysis showed that compared with the normal group,the gastric mucosa of the model group appeared red and swollen,with a large number of blood stasis spots.Pathological sections showed gland cell detachment,cell necrosis,inflammatory cell infiltration,and other phenomena.In the Buzhong Yiqi low-dose decoction group,the gastric mucosa of mice had a small number of petechiae and slight swelling;in the Buzhong Yiqi high-dose decoction group,the gastric mucosa appeared light pink,with no blood stasis observed.Pathological sections showed that the gastric mucosa of the mice in the Buzhong Yiqi decoction group was relatively intact,with glandular tissue relatively neatly arranged,fewer glands shed,and a reduced number of necrotic cells and inflammatory cells.Western blotting results showed increased expression of G6PDH and YY1 proteins in the model group,while the expressions significantly dereased in the Buzhong Yiqi decoction group.Metabolomics analysis identified a total of 715 metabolites in the normal group,model group,and Buzhong Yiqi decoction group.According to principal component analysis and partial least squares-discriminant analysis,the metabolic profiles of the three groups were different.Further analysis revealed 50 differential metabolites in the Buzhong Yiqi decoction group,which had regulatory effects on the model group.The differential metabolites between each group were further enriched and analyzed using the KEGG Pathway database.The results showed that the differential metabolites were involved in serotonergic synapse,histidine metabolism,cyclic adenosine monophosphate(cAMP)signaling pathway,arachidonic acid metabolism,and adipocyte lipolysis regulation,sphingolipid signaling pathways,and other pathways.[Conclusions]Buzhong Yiqi decoction can promote the repair of gastric mucosal damage and relieve plateau stress by regulating 5-hydroxytryptamine synapses,histidine metabolism,cAMP signaling pathways,arachidonic acid metabolism,and other pathways,as well as by regulating the expression of G6PDH and YY1 proteins to alleviate the occurrence of plateau stress gastric ulcer.Due to the plateau environment and local eating habits,HSU often suffers from complex conditions such as blood stasis and phlegm-dampness.This study focused only on Qi deficiency type and conducted a preliminary study on the mechanism of action of Buzhong Yiqi decoction.In the future,further in-depth research is needed on the detailed mechanism of Buzhong Yiqi decoction's action and its effectiveness in treating different conditions such as blood stasis and phlegm.
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