Dynamic observation of the progression of chronic gastritis to gastric cancer in a disease–TCM pattern rat model

Abstract Objective To dynamically observe the progression of chronic gastritis to gastric cancer (GC) in disease-traditional Chinese medicine (TCM) pattern rats to provide data for understanding the disease progression and effective approaches for drug screening and mechanism exploration. Methods Wistar rats were randomly divided into control (n = 96, half female and half male) and model (n = 336, half female and half male) groups. Model rats received free access to N-methyl-N′-nitro-N-nitrosoguanidine (120 μg/mL), sodium deoxycholate (20 mmol/L), and alcohol (45%), and were subjected to intermittent fasting. Mortality rate, body weight, water consumption, food intake, gastric pathology, blood content analysis, and liver and kidney function of model rats were dynamically monitored over 30 weeks. In the 30th week, pattern characteristics were assessed. Gastric pathology and pattern characteristics were observed for an additional 8 weeks to evaluate stability. Results The overall mortality of the model group was 34.82% (33.10% for females and 36.55% for males) at 30 weeks post-intervention. Inflammatory cell infiltration, glandular atrophy, atypical hyperplasia, and GC manifested successively in the gastric mucosa of rats. In model rats, N-methyl-N′-nitro-N-nitrosoguanidine intake was lower in males than in females, whereas pathological changes in the gastric mucosa occurred earlier in females than in males. Notably, gastric mucosal lesions were more severe in males than in females. Our modeling methods maintained stable gastric mucosal lesions for at least 8 weeks after final intervention. The pattern characteristics observed in model rats at the 30th and 38th week were consistent with those of spleen deficiency, blood stasis, and yin deficiency pattern. Blood content and indexes of liver and kidney function in the model group were normal. Conclusion Our findings provide evidence for the pathological stages underscoring the progression of chronic gastritis to GC in disease-TCM pattern rats, which may facilitate development of relevant pharmacotherapies.