Role of NLRP3 inflammasome signaling pathway in hydrogen-rich water treatment of ulcerative colitis in mice
YANG Tao,SHI Yang,LIU Yuan-sheng
Abstract:
Objective To investigate the influences of hydrogen-rich water on ulcerative colitis (UC) mouse as well as the role of the NOD-like receptor protein 3 (NLRP3) inflammasome in this process. Methods A total of 60 healthy male C57BL/6J mice, aged 6-8 weeks and weighing 22-25 g, were divided into four groups in random (n=15): control group (C group), UC group, hydrogen-rich water group (UC+H2 group), and hydrogen-rich water plus NLRP3 agonist BMS986299 group (UC+H2+BMS986299 group). The UC mouse model was established by free drinking of 4% dextran sodium sulfate (DSS). The UC+H2 group and UC+H2+BMS986299 group were treated with hydrogen-rich water by gavage, while the UC+H2+BMS986299 group was intervened with BMS986299 via tail vein injection. After the gavage treatment with hydrogen-rich water, the disease activity index (DAI) was observed, colon pathological changes were detected by HE staining, IL-1β and IL-18 concentrations in serum and colon were measured by ELISA, and the protein expression of NLRP3 inflammasome in colon were detected by Western-blot. Results In comparison with the C group, the UC group displayed obvious pathological damage in colonic tissues, with significantly higher DAI scores, levels of IL-1β and IL-18 in serum and colonic tissues, and protein expression of NLRP3 inflammasome in colonic tissues (P <0.05). In comparison with the UC group, the UC+H2 group presented significantly reduced pathological damage in colonic tissues, DAI scores, levels of IL-1β and IL-18 in serum and colonic tissues, and protein expression levels of NLRP3 inflammasome in colonic tissues (P <0.05). Compared with the UC+H2 group, the UC+H2+BMS986299 group exhibited significantly increased pathological damage in colonic tissues, DAI scores, levels of IL-1β and IL-18 in serum and colonic tissues, and protein expression of NLRP3 inflammasome in colonic tissues (P <0.05). Conclusion Hydrogen-rich water benefits DSS-induced UC in mice, whose mechanism may be associated with the downregulation of NLRP3 inflammasome expression, thereby alleviating systemic and colonic tissue inflammatory responses.
