[Nuclear magnetic resonance-based metabolomics revealed metabolite profiles participate in intervention effect of refined moxibustion in gastric ulcer model rats].

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 (=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 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 (<0.01, <0.05), and further notably up-regulated in the acupoint moxibustion group (<0.001, <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 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.