期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 215, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2021.112161
关键词
Ulcerative colitis (UC); Neutrophil extracellular traps (NETs); Staphylococcal nuclease (SNase); Calcium alginate
资金
- National Natural Science Foundation of China (China) [81973224]
- Double FirstClass University project (China) [CPU2018GF/GY16, CPU2018GF/GY17]
Oral administration of ALG-SNase can reduce intestinal NET levels in UC mice, alleviate clinical colitis and tissue inflammation, and decrease intestinal permeability. Furthermore, SNase nanoparticles regulate the expression levels of proinflammatory cytokines, suggesting a potential therapeutic role for UC treatment.
Recent studies have revealed that neutrophil extracellular traps (NETs) may contribute directly to the initiation of ulcerative colitis (UC), a typical inflammatory bowel disease (IBD) characterized by mucosal damage. Staphylococcal nuclease (SNase), a nonspecific phosphodiesterase, has a strong ability to degrade DNA. Here we investigate whether intestinal NET degradation with an oral preparation of SNase can ameliorate dextran sulfate sodium (DSS)-induced UC in mice. SNase encapsulated with calcium alginate (ALG-SNase) was formulated using crosslinking technology with sodium alginate and calcium chloride. ALG-SNase were orally administered to DSSinduced UC mice, and their therapeutic efficacy was evaluated. The expression of inflammatory cytokines and biomarkers of NETs was also assessed, as well as the intestinal permeability in mice. The results showed that ALG-SNase nanoparticles were successfully prepared and delivered to the colon of UC mice. In addition, oral administration of ALG-SNase nanoparticles decreased NET levels in the colon and effectively alleviated the clinical colitis index and tissue inflammation in UC mice. Moreover, the SNase nanoparticles reduced intestinal permeability and regulated the expression of proinflammatory cytokines. Furthermore, the markers of NETs were strongly correlated with the expression levels of tight junction proteins in colon tissue. In conclusion, our data showed that oral administration of ALG-SNase can effectively ameliorate colitis in UC mice via NET degradation and suggested SNase as a candidate therapy for the treatment of UC.
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