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Abstract
Background To experimentally evaluate the therapeutic effect of a novel oral anti-fibrosis drug, Nintedanib, on experimental animal models of intestinal fibrosis induced by chemical drugs in simulated inflammatory bowel disease (IBD).
Methods An experimental animal model of intestinal fibrosis in IBD was established using chemical drug induction. After modeling, the experimental mice were randomly divided into 4 groups with 10 mice each: group A was treated with saline as a blank control group, group B was treated with sulfasalazine, group C was treated with prednisone, and group D was treated with Nintedanib. Each group was given medication at regular intervals, twice daily. At the end of the experiment, count and compare the colon weight/length ratio, the degree of colonic fibrosis in each group of mice, and detect serum inflammation and fibrosis-related cytokines γ- Interferon (IFN-γ), Interleukin-2 (IL-2), Interleukin-10 (IL-10), Tumor Necrosis Factor (TNF-α) and transforming growth factor (TGF-β).
Results The ratio of colon weight to length and the degree of colonic fibrosis in the Nintedanib group were significantly lower than those in the other groups (P<0.05) (IDDF2024-ABS-0070 Figure 1. Masson staining of colon tissue of animals in each experimental group after intervention treatment. Fibrous tissue can be shown as blue colored, while other tissues such as muscle tissue and epithelial tissue are shown as red. A: Blank control group; B: Sulfasalazine treatment group; C: Prednisone treatment group; D: Nintedanib treatment group. The results showed that the level of blue stained fibrotic tissue in colon tissue in group D was significantly lower than that in other groups). The level of TGF-βin Nintedanib group was significantly lower than those of other groups (P<0.05). The levels of TNF-α, IFN-γ and IL-2 in Nintedanib group, sulfasalazine group and prednisone group were significantly lower than that of the blank control group (P<0.05), while the level of IL-10 was significantly higher than that of the blank control group (P<0.05) (IDDF2024-ABS-0070 Figure 2. Levels of various inflammatory and fibrotic cytokines in serum of animals in each experimental group after intervention treatment. A: IFN-γ; B: IL-2; C: IL-10; D: TNF-α; E: TGF-β. The results showed that: TGF- β in group A, B and C similarly, group D was significantly reduced, but the levels of inflammatory cytokines in colon tissue in groups B, C, and D were significantly different from those in the blank control group).
Masson staining of colon tissue of animals in each experimental group after intervention treatment. Fibrous tissue can be shown as blue colored, while other tissues such as muscle tissue and epithelial tissue are shown as red. A: Blank control group; B: Sulfasalazine treatment group; C: Prednisone treatment group; D: Nintedanib treatment group. The results showed that the level of blue stained fibrotic tissue in colon tissue in group D was significantly lower than that in other groups
Levels of various inflammatory and fibrotic cytokines in serum of animals in each experimental group after intervention treatment. A: IFN-γ; B: IL-2; C: IL-10; D: TNF-α; E: TGF-β. The results showed that: TGF- β in group A, B and C similarly, group D was significantly reduced, but the levels of inflammatory cytokines in colon tissue in groups B, C, and D were significantly different from those in the blank control group
Conclusions The results of experimental animal model therapy suggest that Nintedanib has a certain anti-inflammatory effect on colon tissue of IBD in vivo, and its anti-fibrosis effect is stronger than traditional therapeutic drugs. If it is further promoted to clinical treatment, it may provide a new option for the treatment of intestinal fibrosis caused by IBD.