Effect of Ulinastatin upon Inflammation and TLR4/NF-κB Signaling Pathway in Ulcerative Colitis Rats Model

OBJECTIVE To observe the effect of ulinastatin on ulcerative colitis (UC), and its intervention effect on toll-like receptor 4 (TLR4)/NF-kappa B (NF-κB) signaling pathway, thus to investigate its possible mechanism. METHODS Trinitrobenzene sulfonic acid (TNBS)/ethanol enema method was used to set up the UC rat model. Eighty male Wistar rats were randomly divided into blank group; model group, ulinastatin group(received ulinastatin 50 000 U·kg^-1·d^-1 by intraperitoneal injections), corticosteriod group(prednisone tablets 6 mg·kg^-1·d^-1 intragastric administration), with 20 rates in each group. All the rats were sacrificed one week after modeling, the gross score of colonic mucosa (CMDI score) and histological grading of each group were observed. The serum levels of TNF-α were determined by ELISA. Expression of TLR4 and NF-κB in colon mucosa were further detected by immuno-histochemistry. RESULTS The colon gross morphological damage, and the histological score of the model group rats were significantly higher than those of the blank group (all P<0.01), indicated successful establishment of UC model. Compared with the model group, the CMDI score and pathological score in ulinastatin group were decreased(all P<0.05). There were no differences of the CMDI score and pathological score between the corticosteriod group and ulinastatin group. The levels of serum TNF-α in model group rats were significantly higher than those of the blank group rats(P<0.01). Compared with the model group, the serum levels of TNF-α in ulinastatin group were significantly decreased(P<0.05), which were no significant differences between the corticosteriod group and the ulinastatin group. Compared with the blank group, the expression of NF-κB and TLR4 in model group significantly enhanced (P<0.01), which in ulinastatin group were lower than the model group (all P<0.05). The expression of NF-κB in ulinastatin group was lower than the corticosteriod group (P<0.05), and the expression of TLR4 had no significant difference with corticosteriod group. CONCLUSION Ulinastatin can alleviate ulcerative colitis rat intestinal inflammatory reaction, showing a therapeutic effect for UC. The mechanism may be related with inhibiting the expression of TLR4 and NF-κB, and reducing inflammation factor of TNF-α release.