Objective To investigate the effect of refined moxibustion on expression of gastric mucosal epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF)

and changes of metabolite profiles in gastric ulcer(GU) rats

so as to analyze its mechanism underlying improvement of GU. Methods Male SD rats were randomized into control

model

acupoint moxibustion groups(n=6 per group). The GU model was induced by cold-restraint stress. The ignited refined moxa was applied to bilateral “Liangmen”(ST21) and “Zusanli”(ST36) for 3 cones/acupoint

once daily for 7 days. Then

we employed

1

H NMR-based metabolomics approach to analyze the metabolic profiles of serum and stomach tissue samples. The conventional histopathological changes of the gastric mucosa were observed by H.E. stain and the expressions of EGFR and VEGF in the gastric mucosa were detected by immunohistochemistry. Results Compared to the control group

the expression levels of EGFR and VEGF were significantly increased in the model group(P

<

0.01

P

<

0.05)

and further notably up-regulated in the acupoint moxibustion group(P

<

0.001

P

<

0.01). Results of H.E. staining showed damage of the folds of gastric mucosa

disordered arrangement of the glands

infiltration of inflammatory cells and unclear structure of gastric mucosa in the model group

which was relatively milder in the acupoint moxibustion group. 1H NMR-based metabolomics approach to analyze the metabolic profiles of serum and stomach tissue samples. The conventional histopathological changes of the gastric mucosa were observed by H.E. stain and the expressions of EGFR and VEGF in the gastric mucosa were detected by immunohistochemistry. Results Compared to the control group

the expression levels of EGFR and VEGF were significantly increased in the model group(P

<

0.01

P

<

0.05)

and further notably up-regulated in the acupoint moxibustion group(P

<

0.001

P

<

0.01). Results of H.E. staining showed damage of the folds of gastric mucosa

disordered arrangement of the glands

infiltration of inflammatory cells and unclear structure of gastric mucosa in the model group

which was relatively milder in the acupoint moxibustion group.

1

H-NMR technical analysis showed that in comparison with the control group

11 and 11 metabolites in the stomach extract and plasma were increased

10 in the gastric tissue and 3 in the plasma were decreased in the GU model group; while in comparison with the model group

17 differently expressed metabolites in the gastric extract and 10 metabolites in the plasma restored to their levels of control group after the acupoint moxibustion intervention. These metabolites participate in 12 metabolic pathways including glycine

serine and threonine metabolism

glutathione metabolism

glycine metabolism

alanine

aspartic acid and glutamic acid metabolism

purine metabolism

glyoxylic acid and digarboxylic acid metabolism

biosynthesis of aminoacyl-tRNA

amino sugar and nucleotide sugar metabolism

cysteine and methionine metabolism

citrate cycle

pyruvate metabolism

and the mutual conversion of pentose and glucuronate

suggesting their involvement in moxibustion-induced improvement of GU. Conclusion Refined moxibustion at ST21 and ST36 can up-regulate the expression of EGFR and VEGF in the gastric mucosa and lessen gastric mucosal injury

which may be related to its effects in reducing GU-induced metabolic disorders

including sugar

purine

amino acid

and phospholipid metabolism and antioxidant defense system.