Intestinal mucosal injury induced by obstructive jaundice is associated with activation of TLR4/TRAF6/NF-κB pathways.

Abstract

OBJECTIVES:To investigate the role of TLR4/TRAF6/NF-κB pathways in intestinal mucosal injury induced by obstructive jaundice (OJ). METHODS:A total of 100 male C57BL/6J mice were randomly assigned to two groups: (I) sham operation (SH); (II) OJ. The mice were sacrificed before operation and on the 1st, 3rd, 5th and 7th day after operation. The blood and terminal ileum were simultaneously collected under the aseptic condition for further detection. RESULTS:In the SH group, TLR4 protein and mRNA rarely expressed in the intestinal mucosa of the mice and there were no significant differences at different time points (p>0.05). By contrast, in the OJ group TLR4 protein (0.12±0.06, 0.16±0.08, 0.27±0.10, 0.35±0.12 and 0.41±0.13, respectively) and mRNA (0.49±0.19, 0.62±0.23, 0.98±0.32, 1.42±0.41 and 1.72±0.49, respectively) increased gradually with the extension of time (p<0.05). Also in the OJ group, the levels of DAO and endotoxin in plasma as well as the expressions of NF-κB and caspase-3 increased gradually with the extension of time, showing positive correlation with the expression of TLR4 (p<0.05). CONCLUSIONS:The expression of TLR4 was significantly up-regulated in the distal ileum of mice with OJ. Activation of the TLR4/TRAF6/NF-κB pathways was involved in the occurrence and development of intestinal mucosal injury and endotoxemia in mice with OJ.