Different Mechanism and Efficacy of Dextran-Sodium Sulfate and 2,4,6-Trinitrobenzene Sulphonic Acid in Modeling Ulcerative Colitis in C57BL/6 Mice

Abstract

Background and Aims: Dextran-sodium sulfate and 2,4,6-trinitrobenzene sulphonic acid are common modeling methods in studying ulcerative colitis. Little attention has been paid to the mechanism differences between the two approaches. Here, we aim to compare the mechanisms and efficacy of these two models and wish to provide fundamental proves for choosing ideal ulcerative colitis models. Methods: Dextran-sodium sulfate and 2,4,6-trinitrobenzene sulphonic acid were applied to induce the colitis in C57BL/6 mice for seven days. Body weight and disease activity index were assessed. Hematology was detected by routine blood test. Histopathology was analyzed by hematoxylin-eosin staining section. Enzyme-linked immunosorbent assay, Western blot and quantitative real-time PCR were used to detect the cytokines protein levels and mRNA levels. Flow cytometry were used to detect the cycles and subsets of splenic cells. Results: Dextran-sodium sulfate induced colitis in C57BL/6 mice showed higher acute immune activities, while 2,4,6-trinitrobenzene sulphonic acid induced colitis showed chronic immune activities with high platelet amounts and activation. Dextran-sodium sulfate is more suitable for modeling acute ulcerative colitis. On the contrary, 2,4,6-trinitrobenzene sulphonic acid is more appropriate for modeling chronic ulcerative colitis. Conclusions: Dextran-sodium sulfate treatment within 7 days in C57BL/6 mice is a suitable experimental model for studying human acute ulcerative colitis with immune response, fecal blood and acute pathogenic damage. Conversely, 2,4,6-trinitrobenzene sulphonic acid treatment within 7 days is more appropriate for studying human chronic ulcerative colitis with hypercoagulable state, IL-2 over-expression state and chronic pathogenic damage.