Gastritis Model

Indication / Application

Efficacy validation of anti-H. pylori regimens (including triple/quadruple therapies and novel targeted antimicrobials), screening of mucosal repair agents, preclinical evaluation of drugs arresting or reversing chronic atrophic gastritis, and mechanistic research on gastric carcinogenesis pathways.

Modeling Method

1. Helicobacter pylori-Induced Gastritis Model (Infectious & Inflammatory):

• C57BL/6 mice or Mongolian gerbils are inoculated via oral gavage with clinically isolated, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) positive H. pylori strains (e.g., SS1 or PMSS1). This establishes persistent gastric colonization, triggering robust mucosal neutrophil and lymphocyte infiltration within 4 to 12 weeks.

1. Chronic Atrophic Gastritis (CAG) Model (Chemical & Dietary):

• Rodents are administered combined chemical agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium deoxycholate, or hot water via gavage, combined with irregular starvation. Over 12 to 24 weeks, this multi-hit approach reliably drives mucosal thinning, glandular loss, and atypical hyperplasia.

1. Autoimmune Gastritis Model:

• Induced via thymectomy or targeted immunization with gastric H+/K+-ATPase to replicate autoimmune destruction of parietal cells, leading to profound achlorhydria and glandular atrophy.

Clinical Relevance

• Pathological Coherence: The H. pylori model matches human active chronic gastritis, displaying a shift from acute neutrophilic infiltration to chronic lymphofollicular hyperplasia.

• Pre-malignant Cascade: The MNNG-induced CAG model faithfully demonstrates the "Correa Cascade" (normal mucosa → chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia), offering a crucial translational window for drugs designed to halt gastric cancer progression.

• Human-Scale Evaluation: Bama mini-pig models are utilized for chronic mucosal irritation testing and localized endoluminal therapy, presenting clinical-grade stomach volumes and mucosal folds.

Key Evaluation Endpoints

Microbiological & Colonization Diagnostics (H. pylori Models)

• Quantitative Colonization Density: Determination of viable bacterial load (CFU/g of gastric tissue) via selective agar plating.

• Rapid Urease Test (RUT) & PCR: Real-time validation of active urease activity and H. pylori genomic DNA (ureA/ureB) presence.

Macroscopic & Histopathology 

• Glandular & Mucosal Morphometry: High-resolution histopathological scoring (Sydney System) of inflammatory activity, chronicity, glandular atrophy, and intestinal metaplasia using H&E and Alcian Blue-PAS staining.

• H. pylori Visualization: Modified Giemsa or Warthin-Starry silver staining to pinpoint helical bacteria adhering to the gastric luminal epithelium.

• Epithelial Apoptosis & Proliferation: IHC analysis of Ki-67, PCNA, and TUNEL to evaluate mucosal turnover kinetics.

Molecular, Inflammatory & Secretory Profiling

• Gastric Secretory Parameters: Measurement of gastric pH, total acid output, and serum gastrin-17 levels (to evaluate G-cell function and atrophy-induced hypergastrinemia).

• Localized Cytokine Profiling: Quantification of mucosal Th1/Th17-driven pro-inflammatory cytokines (such as IFN-gamma, IL-1beta, IL-8/CINC, IL-17, and TNF-alpha) via RT-qPCR, Western Blot, or multiplex ELISA.

• Oxidative Stress Assays: Measurement of mucosal Myeloperoxidase (MPO) activity (neutrophil infiltration marker), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) levels.