Abstract

This study was performed to study the effects of astragalus polysaccharides (APS) in the treatment of ulcerative colitis (UC), and to explore whether myeloid-derived suppressor cells (MDSC) involve in this process. UC model was established by dextran sulfate sodium salt (DSS) inducement in mouse. Then the effects of APS on UC was evaluate at the levels of cytology and molecular biology: exploring the influence of APS on MDSC by analyzing the levels of MDSC before and after the treatments of APS; evaluating the therapeutic effects of APS on UC by pathologic histology. Data showed that the levels of MDSC in bone marrow, spleen, peripheral blood of UC mice were significantly decreased after intervention with APS, indicating APS inhibited the level of MDSC significantly. After depletion bone marrow cells in mice, we further found that the therapeutic effects of APS in MDSC- group was significantly reduced compared with MDSC+ group. It was discovered through pathological analysis that, compared with UC model group, APS intervention group mainly manifested as reduced infiltrating acute and chronic inflammatory cells, necrotic epithelial cells and epithelial ulceration. Therefore, APS could reduce the inflammatory cell infiltration in colonic tissues of UC model mice, repair the damaged colonic mucosa, and promote ulcer healing. In conclusion, APS has a potential application in the treatment of ulcerative colitis, and is dependent or partially dependent on MDSC to achieve this effects.

Highlights

  • Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis (UC), which is associated with unclear etiology and pathogenesis

  • The myeloid-derived suppressor cells (MDSC) in bone marrow of normal group accounted for 25.7%, while those in UC model group took up 38.0%, and the proportion in the bone marrow of UC model group was apparently higher than that in normal group (P

  • The MDSCs in bone marrow of astragalus polysaccharides (APS) intervention group had accounted for 26.5%, which was markedly declined compared with that in model group, and the difference was significant (P

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Summary

Introduction

Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis (UC), which is associated with unclear etiology and pathogenesis. Immune factor has been well recognized as a crucial factor in the IBD pathogenesis, which has always been the research hotspot. The suppression of MDSCs is mainly related to the production of arginase and inducible nitric oxide synthase (iNOS). It can promote Treg differentiation, suppress T-cell response and weaken the NK function, exerting a key role in tumor immunity and inflammatory response. With the deepening of basic research, the expression profile and clinical significance of MDSCs in disease have attracted attention [4].

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