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Proteomics analyses of Xiaopi granules in MNNG-induced gastric epithelial dysplasia rat model by LC-MS.

OBJECTIVE
Xiaopi granules have been shown to ameliorate gastric epithelial dysplasia in patients. However, the therapeutic mechanism is unclear. Herein, the proteomics method was applied to identify the differentially expressed proteins and related pathways.


METHODS
Sixty male Sprague-Dawley (SD) rats were randomly divided into four groups: control (C group, n=10), model (M group), Xiaopi granules (X group), and vitacoenzyme (V group). The rat gastric epithelial dysplasia model was established by intragastrically administering N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and ranitidine, and drinking 0.05% ammonia solution. After 12 weeks, the stomach tissue was analyzed by H&E staining and proteomics analyses. Western blot analysis was applied to further validate the proteomics results.


RESULTS
Compared to the M group, levels of 326 and 350 proteins were altered significantly in the X and V groups (1.5-fold, P<0.05), which were significantly enriched in digestion, metabolism, coagulation, and cell apoptosis. CELA2A, GHRL, NDUFB9, and PGC were significantly upregulated (P<0.0001), while CLCA1, PLG, and DAC2 were downregulated (P<0.001 or P<0.0001) in the M group vs. the C group. The change in the above proteins could be reversed after the treatment of Xiaopi granules or vitacoenzyme tablets.


CONCLUSION
Xiaopi granules improve ameliorated gastric epithelial dysplasia by intervening in digestion, metabolism, blood coagulation, cell apoptosis, and other related pathways.