New Drug Development Services
Inflammatory Bowel Disease (IBD) Model
- Categories:Non-tumor model and drug efficacy evaluation platform
- Time of issue:2024-07-19 16:31:42
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Inflammatory Bowel Disease (IBD) is a group of chronic and relapsing intestinal inflammatory diseases, mainly including ulcerative colitis (UC) and Crohn's Disease (CD). In order to meet the needs of preclinical research on the etiology, pathogenesis and efficacy of newly developed drugs, a variety of animal models have been widely used, such as chemically induced models, spontaneous models, genetically modified models and adoptive T cell transfer. Models etc. Among them, the animal model induced by Dextran Sulfate Sodium Salt (DSS) is the most widely used chemically induced IBD model. DSS can damage the tight junctions and basement membrane of colonic epithelial cells, thereby increasing intestinal permeability, causing intestinal flora and other antigens to enter the submucosa and systemic circulation, activating immune-inflammatory responses and inducing colitis symptoms. The animals showed clinical symptoms such as abdominal pain, diarrhea, bloody stools, weight loss, and fatigue. The advantages are simple operation, high success rate, and good reproducibility. Its symptoms and histological changes are similar to human clinical ulcerative colitis, and both acute and chronic colon can be made by giving animals free drinking water solutions of different concentrations of DSS. The inflammation model is an ideal model for studying the pathogenesis and drug efficacy of UC.
InnoModels Biotechnology has established a stable DSS-induced IBD disease model in C57BL/6J mice, which can be used for preclinical research and drug efficacy evaluation of ulcerative colitis.
Case: DSS-induced IBD mouse disease model is used to evaluate the efficacy of cyclosporin A (Ciclosporin A, CsA)
1. Preventive administration
Modeling and efficacy evaluation process:
Evaluation indicators:
1. Weight
Record weight changes once a day
2. Disease activity index (DAI) score
DAI = (weight loss score + stool character score + blood in stool score)/3. 1) Weight loss score: weight loss percentage (the weight remains unchanged as 0, 1-5 is 1 point, 5-10 is 2 points, 10-20 3 points, greater than 20 is 4 points); 2) Stool character score: stool viscosity (normal is 0, soft stool is 1 point, mucoid stool is 2 points, and thin liquid stool is 3 points); 3) Blood in the stool score : Stool bleeding (normal 0 points, light blue occult blood indicator is 1 point, blue occult blood indicator is 2 points, dark blue occult blood indicator is 3 points, naked blood in the stool is 4 points).
DAI can quantitatively analyze the disease in mice. Mice were scored once a day for DAI.
3. Colon length
At the end of the experiment, colon length was measured.
4. Visual intestinal mucosal injury (CMDI) score
At the end of the experiment, the mice were scored by CMDI. CMDI scoring standard: 0 points for no damage; 1 point for mild congestion, edema, smooth surface, no erosion or ulcer; 2 points for congestion and edema, rough and granular mucosa, erosion or intestinal adhesion; 2 points for high degree of congestion and edema, mucosa There is necrosis and ulcer formation on the surface, and the maximum longitudinal diameter of the ulcer is less than 1.0 cm. If the intestinal wall is thickened or there is necrosis and inflammation on the surface, it is scored as 3 points. On the basis of 3 points, the maximum longitudinal diameter of the ulcer is greater than 1.0 cm or the entire intestinal wall is necrotic as 4 points. point.
5. Pathological examination
After the experiment, the colon tissue was removed, HE stained, and pathologically examined.
G1 Vehicle A small number of lymphocytes are scattered in the lamina propria of the intestinal mucosa, and a small number of free neutrophils are seen.
G5-DSS: Focal ulcer formation in the intestinal mucosa, inflammatory exudate and granulation tissue proliferation, and more inflammatory cells (including more eosinophils, lymphocytes, neutrophils, histiocytes, etc.) and Lymph nodes.
G3 DSS+CsA A small number of lymphocytes are scattered in the lamina propria of the intestinal mucosa, and a small amount of free pancreatic tissue is seen.
Summary: Experimental data show that compared with the non-modeling group (G1 Vehicle), the animal weight of the modeling group (G2 DSS) has decreased, and the DAI and CMDI scores have increased significantly. The length of the colon has been significantly shortened on Day 7; ulcer formation can be seen. Inflammatory exudate and granulation tissue proliferated, with more inflammatory cell infiltration and lymph nodes. The body weight of the animals in the drug administration group (G3 DSS+CsA) did not change significantly; DAI and CMDI scores increased slightly; colon length was shortened on Day 7, but the degree of shortening was less than that of the modeling group (G2 DSS); pathological results showed significant colon symptoms Remission, similar to the pathological structure of the non-model group (G1-Vehicle). This shows that the DSS-induced C57BL/6 mouse inflammatory bowel disease model was successfully modeled, and the CsA preventive treatment regimen significantly alleviated the clinical symptoms of the DSS-induced C57BL/6 mouse inflammatory bowel disease model.
2. Therapeutic administration
Modeling and efficacy evaluation process:
Evaluation indicators:
1. Weight
Record weight changes once a day
2. Disease activity index (DAI) score
At the end of the experiment, the mice were DAI scored.
3. Colon length
At the end of the experiment, colon length was measured.
4. Visual intestinal mucosal injury (CMDI) score
At the end of the experiment, the mice were scored by CMDI.
5. Pathological examination
After the experiment, the colon tissue was removed, HE stained, and pathologically examined.
G1 Vehicle A small number of lymphocytes are scattered in the lamina propria of the intestinal mucosa, and a small number of free neutrophils are seen.
G4 DSS The intestinal mucosa is significantly thinned locally. There are no large intestinal glands in the lamina propria in this area. Slightly more inflammatory cells (lymphocytes, eosinophils, etc.) can be seen. Focal mucosal loss is also seen. No obvious inflammatory reaction and granulation are seen in this area. tissue (considered artifact), see also lymph node.
G2 DSS→CsA Local ulcer formation in the intestinal mucosa, inflammatory exudate and granulation tissue proliferation, and a large number of inflammatory cells (including a large number of neutrophils, lymphocytes, histiocytes, etc.) and lymph nodules, and some glandular epithelium can be seen There were proliferative changes, and some glandular epithelium showed low-grade intraepithelial neoplasia.
Summary: Experimental data show that compared with the non-modeling group (G1 Vehicle), the animals in the modeling group (G4 DSS) continued to decline during the modeling process. After stopping DSS stimulation on Day 7, the body weight recovered; the DAI score on Day 13 was also significantly lower. On Day 7 and Day 13, compared with Day 7 of the modeling group (G5 DSS) in the preventive dosing experiment, the colon length increased and the CMDI score decreased slightly (individual differences are not excluded); pathological results showed a large number of inflammatory cell infiltrates, The intestinal mucosa becomes thinner and ulcers form. The body weight of the animals in the drug administration group (G2 DSS → CsA) continued to decrease during the modeling process. After stopping DSS stimulation on Day 7 and continuing drug administration, the body weight recovered, and the degree of recovery was greater than that in the modeling group (G4 DSS); the DAI score on Day 13 also increased. Significantly lower than Day7, Day13 was longer than the Day7 colon length of the administration group (G3 DSS+CsA) in the preventive administration experiment, and the CMDI score was slightly higher; the pathological results showed that it was similar to that of the colon, but also showed some glandular epithelial hyperplasia. Restorative changes. This shows that the therapeutic dosing regimen of CsA alleviates the weight loss of the DSS-induced C57BL/6 mouse inflammatory bowel disease model, and other clinical symptoms such as fecal viscosity, blood in the stool, colon length and intestinal mucosal damage. Compared with the modeling group, the two groups did not show obvious relief. The relief of symptoms in both groups on Days 7 to 13 mainly relied on stopping DSS stimulation.
In summary, CsA has certain efficacy in the DSS-induced IBD mouse disease model, but preventive administration is more effective.
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InnoModels Biotechnology (Beijing) Co., Ltd.
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