摘要
AIM: To determine the dynamic changes in the expression of matrix metalloproteinases (MMPs) and the endogenous tissue inhibitors of MMPs inhibitors (TIMPs) during hepatic fibrosis induced by alcohol.METHODS: Male Sprague-Dawley rats were randomly divided into normal, 4 d, 2 wk, 4 wk, 9 wk and 11 wk groups, and the model rats were fed with a mixture of alcohol by gastric infusion at the designed time, respectively, then decollated and their livers were harvested for the examination of MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1 and TIMP-2 by immunohistochemistry, zymograghy and Western blotting, respectively.RESULTS: Normal rats had moderate expression of MMP-2,which was decreased in the model rats except in the 11 wk group, where MMP-2 expression slightly increased. MMP-3 had the similar changing pattern to MMP-2 despite weaker expression. MMP-9 expression decreased in the 4 d and 2 wk groups, rose in the 4 wk group, decreased again in the 9 wk group and returned to normal levels in the 11 wk group.MMP-13 expression decreased in the 4 d and 2 wk groups,and returned to normal levels in the 4 wk, 9 wk and 11 wk groups. TIMP-1 expression decreased in the 4 d and 2 wk groups, but sharply increased in the 4 wk group and sustained at a high level even after modeling was stopped for 2 wk. In normal rats TIMP-2 expression was strong. However, it decreased as soon as modeling began, and then gradually rose, but remained to a level lower than that in normal rats even after modeling was stopped for 2 wk.CONCLUSION: MMP-2 may not always expresses at a high level during hepatic fibrosis. MMP-13 and MMP-3 are acutely affected by TIMP-1. In this model TIMP-1 is the most powerful factor imposed on capillarization and peri-sinusoidal fibrosis. TIMP-2 is the most effective regulator on the metabolism of type Ⅳ collagen located in the basement of sinus.
AIM:To determine the dynamic changes in the expression of matrix metalloproteinases (MMPs) and the endogenous tissue inhibitors of MMPs inhibitors (TIMPs) during hepatic fibrosis induced by alcohol. METHODS:Male Sprague-Dawley rats were randomly divided into normal,4 d,2 wk,4 wk,g wk and 11 wk groups,and the model rats were fed with a mixture of alcohol by gastric infusion at the designed time,respectively,then decollated and their livers were harvested for the examination of MMP- 2,MMP-3,MMP-9,MMP-13,TIMP-1 and TIMP-2 by immunoh- istochemistry,zymograghy and Western blotting,respectively. RESULTS:Normal rats had moderate expression of MMP-2, which was decreased in the model rats except in the 11 wk group,where MMP-2 expression slightly increased.MMP-3 had the similar changing pattern to MMP-2 despite weaker expression.MMP-9 expression decreased in the 4 d and 2 wk groups,rose in the 4 wk group,decreased again in the 9 wk group and returned to normal levels in the 11 wk group. MMP-13 expression decreased in the 4 d and 2 wk groups, and returned to normal levels in the 4 wk,9 wk and 11 wk groups.TIMP-1 expression decreased in the 4 d and 2 wk groups,but sharply increased in the 4 wk group and sustained at a high level even after modeling was stopped for 2 wk.In normal rats TIMP-2 expression was strong.However,it decreased as soon as modeling began,and then gradually rose,but remained to a level lower than that in normal rats even after modeling was stopped for 2 wk. CONCLUSION:MMP-2 may not always expresses at a high level during hepatic fibrosis.MMP-13 and MMP-3 are acutely affected by TIMP-1.In this model TIMP-1 is the most powerful factor imposed on capillarization and peri-sinusoidal fibrosis.TIMP-2 is the most effective regulator on the metabolism of type Ⅳ collagen located in the basement of sinus.
