ABSTRACT
Objective To investigate the role and mechanism of simvastatin on colonic fibrosis in rats with 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis.Methods Forty-eight healthy male Sprague-Dawley rats were evenly divided into six groups:control group,TNBS group,simvastatin treated group Ⅰ,group Ⅱ (from zero to 21 days after modeling,simvastatin 5 mg/kg or simvastatin 20 mg/kg treated),group Ⅲ and group Ⅳ (from seven to 21 days after modeling,simvastatin 5 mg/kg or 20 mg/kg treated).Body weight and disease activity index (DAI) of the rats were inspected,and general colon,histological injury and fibrosis were scored.The expressions of collagen types Ⅰ and connective tissue growth factor (CTGF) at mRNA level were detected by reverse transcription-polymerase chain reaction (RT-PCR).The expressions of collagen types Ⅰ,CTGF and phosphorylation of myosin phosphatase target subunit-1 (p-MYPT-1) at protein level were determined by Western blotting.The data were analyzed by one-way ANOVA.Results Compared with control group,the colon length shortened,while colon weight,DAI score,general colon score,histological injury and fibrosis score significantly increased in TNBS group.And the expressions of collagen types Ⅰ also obviously increased.After intervention of simvastatin,both the colon length and weight of rats were improved.The DAI score,general score,histological injury and fibrosis score were lower than those of TNBS group.The expressions of collagen types Ⅰ,CTGF and p-MYPT-1 (group Ⅰ:0.68±0.22 ; group Ⅱ:0.59 ± 0.27 ; group Ⅲ:0.71 ± 0.20 ; group Ⅳ:0.59± 0.25) in colonic tissue were all lower than those of TNBS group (F=5.169,P＜0.05).There were no statistical significance among four groups (al1 P＞0.05).Conclusion Simvastatin can effectively prevent TNBS-induced rat colitis from colonic fibrosis,the mechanism may be related with Rho-kinase inhibition and down-regulation of CTGF over-expression.