Effects of neutrophil elastase inhibitor on acute experimental colitis in mice

Abstract

Objective To study the effects of neutrophil elastase (NE) inhibitor (sivelestat) on acute experimental colitis induced by dextran sulfate sodium (DSS) in mice.Methods A total of twenty-six healthy male BALB/C mice were randomly divided into four groups as follows:normal control group(n=6),experimental control group(n=6,treated with phosphate-buffered saline intraperitoneally for 9 days),low-dose group(n=7,treated with sivelestat 50 mg/kg intraperitoneally for 9 days) and high-dose group(n=7,treated with sivelestat 100 mg/kg intraperitoneally for 9 days).Acute experimental colitis model was generated by giving 5% DSS solution.All mice were sacrificed at 10th day to assess the scores of histological injury in colon tissues.The concentration of NE was examined by enzyme-linked immunosorbent assay (ELISA) in both plasma and cultured supernatant of colonic mucosa.The expression of NE in distal colon was analyzed by Western blotting.Results The colonic histological injury score in experimental control group (12.00±2.45) was markedly increased compared with that in normal control group(1.88±0.83,P＜0.0 1).There was a significant difference in scores of colonic histological injury between low-dose group (10.17±1.17) and high-dose group (5.00±1.15,P＜0.05),however,they were both lower than that in experimental control group and higher than that in normal control group (P＜0.05).Compared with normal control group,the concentrations of NE in plasma,and cultured supernatant of colonic mucosa and the expression of NE in distal colon were increased in experimental control group (P＜0.05).And those in low-dose group were higher than those in normal control group (P＜0.05),but were little decreased in comparison with experimental control group (P＞0.05).Whereas those in high-dose group,which showed no significant difference with normal control group (P＞0.05),were significantly decreased compared with experimental control group and low-dose group (P＜0.05).Conclusions Sivelestat,a specific NE inhibitor,may alleviate the DSS-induced experimental colitis,in which high-dose is more effective than low-dose.It suggests that NE may be involved in the pathogenesis of ulcerative colitis. Key words: Colitis; ulcerative; Leukocyte elastase; Diease model; animal