[Effects of nuclear factor-kappaB siRNA upon dextran sulphate sodium-induced colitis murine model].

Objective: To investigate the effects of nuclear factor-kappaB (NF-kappaB) siRNA upon dextran sulphate sodium (DSS)-induced colitis.

Methods: Thirty-six BALB/C mice were randomly divided into 4 groups: normal control group, NF-kappaB siRNA, scrambled siRNA and DSS group. Colitis was induced by treatment with 5% DSS in drinking water and evaluated by disease activity index (DAI) and histological score. The tumor necrosis factor (TNF-alpha) level of colonic mucosa was measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB p65 expression was determined by immunohistochemical staining.

Results: Compared with the scrambled siRNA (DAI 3.42 +/- 0.67, histological score 4.65 +/- 1.53) and DSS group (3.73 +/- 0.55, 4.47 +/- 1.52), a significant decrease was observed in DAI (2.31 +/- 0.26) and histological score (2.19 +/- 0.77) in mice with NF-kappaB p65 siRNA (both P < 0.05). The expression of NF-kappaB p65 and TNF-alpha [(266 +/- 35) pg/ml] in mice with DSS-induced colitis was significantly reduced after treatment with NF-kappaB p65 siRNA (P < 0.05) in comparisons with the scrambled siRNA [(412 +/- 51) pg/ml] and DSS group pg/ml [(449 +/- 44) pg/ml].

Conclusion: NF-kappaB p65siRNA shows protective effects upon the mice with DSS-induced colitis. Blockade of NF-kappaB pathway by NF-kappaB p65 siRNA may serve as a novel gene therapy for ulcerative colitis.