Jian-Pi-Yi-Qi-Fang ameliorates chronic atrophic gastritis in rats through promoting the proliferation and differentiation of gastric stem cells

BACKGROUND: Jian-Pi-Yi-Qi-Fang (JPYQF) is a traditional Chinese medicine (TCM) herbal formula for treating chronic atrophic gastritis (CAG) in the clinic; however, its related mechanism remains unclear. The purpose of this study was to explore the potential mechanisms of JPYQF in treating CAG by examining proteins and genes related to the proliferation and differentiation of gastric stem cells and Wnt signaling. METHODS: A CAG model was established in Sprague-Dawley (SD) rats which were induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and ranitidine. We randomly divided 25 CAG rats into 5 groups: the model group, positive drug group, low-dose group of JPYQF (JPYQF-L), middle-dose group of JPYQF (JPYQF-M), and high-dose group of JPYQF (JPYQF-H), with 5 rats of the same age classified into the control group. The body weight of rats was measured and their gastric morphology was visually assessed. Furthermore, pathological analysis of rat gastric tissue was performed. The expression levels of proteins and genes associated with the proliferation and differentiation of gastric stem cells and Wnt signaling were measured via immunohistochemistry and reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: Compared with the model group, treatment with JPYQF increased the body weight of the rats, and relieved the gastric atrophy and inflammation. Compared with the control group, the protein and messenger RNA (mRNA) expression levels of gastric stem cell proliferation and differentiation markers Lgr5, Sox2, Ki67, PCNA, Muc5AC, and Wnt signaling initiator Wnt3A and enhancer R-spondin-1 (Rspo1) were decreased in the model group. Treatment with JPYQF increased the protein and mRNA expression levels of these markers. CONCLUSIONS: The Wnt signaling of CAG rats may be in a low activation state, which inhibits the proliferation and differentiation of gastric stem cells, so that gland cells cannot be replenished in time to repair the damaged gastric mucosa. The TCM formula JPYQF could enhance Wnt signaling to promote the restricted proliferation and normal differentiation of gastric stem cells, thereby improving gastric mucosal atrophy in CAG rats, which provides a novel and robust theoretical basis for CAG treatment.