Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction

摘要

AIM: To investigate whether dimethyl sulfoxide(DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatoryresponse syndrome and multiple organ dysfunction syndrome.METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline(SS group); sham with administration of DMSO(SD group); zymosan with administration of normal saline(ZS group); and zymosan with administration of DMSO(ZD group). Each group contained three subgroups according to 4 h,8 h,and 24 h after surgery. At 4 h,8 h,and 24 h after intraperitoneal injection of zymosan(750 mg/kg),the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha(TNF-α) and interleukin(IL)-10] and oxides(myeloperoxidase,malonaldehyde,and superoxide dismutase) were examined. The levels of diamine oxidase(DAO) in plasma and intestinal mucosal blood flow(IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay. The intestinal epithelial tight junction protein,ZO-1,was observed by immunofluorescence.RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration(P < 0.05). DMSO decreased the content of malondialdehyde(MDA) and increased the activity of superoxide dehydrogenase(SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group,respectively(P < 0.05). DMSO alleviated injury in intestinal villi,and the gut injury score was significantly lower than the ZS group(3.6 ± 0.2 vs 4.2 ± 0.3,P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group(65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L,P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group(P < 0.05).CONCLUSION: DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.