ABSTRACT
Synaptotagmin 1 (Sytl) is a member of the Synaptotagmin family and plays a role in neurotransmitter vesicle transport and exoeytosis. It has been reported that Sytl appears to be expressed in the intestinal epithelium, but the biological function of Sytl in colitis remains poorly understood. This study aimed to investigate the effects of Sytl in the inflammatory response and intestinal epithelial regeneration in colitis using Sytl transgenic mice and dextran sulfate sodium (DSS)-induced ulcerative colitis mode. qRT-PCR and Western blotting were employed to analyze the dynamic changes of Sytl in colitis. H&E staining, immunostaining and Western blotting were used to explore the roles of Sytl in the inflammatory response and in the regeneration and repair of intestinal epithelium in colitis. The results showed that the expression level of Sytl was indeed high in the colonic epithelium of wild-type mice and the intestinal epithelial cells of the adjacent tissues of colorectal cancer patients. Consistently, DSS-induced inflammation progressively resulted in marked upregulation of Sytl in the colon (P<0.01). In DSS-induced colitis, both the body weight loss and colonic shortening were dampened in Sytl loss-of-function mice compared with the control group (P < 0.05), while the number of regenerated crypts and Ki67 proliferating cells were also increased (P<0.01). Additionally, there were less infiltration of CD45 immune cells and F 4/80 macrophages and the expression of pro-inflammatory cytokines IL-6, TNFα and I L l-β, which were related with the severity of inflammation in the inflammatory bowel disease (I B D), were significantly decreased after Sytl deletion (P<0.05). Immunohistochemistry staining and Western blotting results further showed that IL-6 and p-STAT3 was significantly downregulated in Sytl knockdown mice (P<0.05). Taken together, these results suggested that knocking-down of Sytl may improve colitis by inhibiting the IL6/STAT3 signaling pathway.
ABSTRACT
Objective To determine the length of warm ischemic (WI) tolerance in bronchial graft from non-heart-beating donors. Methods Forty-eight rats were randomly divided into 4 groups (each group having 12 rats) according to different WI durations including WI-0 min (group A), WI-30 min (group B), WI-45 min (group C) and WI-60 min (group D). In each group, the tracheae from 6 rats were respectively imbedded in greater omentum of other 6 rats, and 14 days later, the transplanted tracheae were taken from recipients to evaluate epithelial thickness and regeneration. Results Epithelial thickness and the degree of epithelial regeneration had no significant difference (P >0. 05) between the syngeneic control group and the WI-30 minutes group. All of the grafts with WI duration of 45 min were viable, but the epithelium was significantly thinner than that in the syngeneic control group (P<0. 05). However all of the grafts with WI duration of 60 min showed lower viability rate. Conclusion The time limits of tolerance to WI of tracheal grafts from NHBDs may be 45 min.