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首页> 外文期刊>World Journal of Gastroenterology >Dynamic changes in the expression of matrix metalloproteinases and their inhibitors, TIMPs, during hepatic fibrosis induced by alcohol in rats
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Dynamic changes in the expression of matrix metalloproteinases and their inhibitors, TIMPs, during hepatic fibrosis induced by alcohol in rats

机译：酒精引起的大鼠肝纤维化过程中基质金属蛋白酶及其抑制剂TIMPs表达的动态变化

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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 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.
机译：目的：确定酒精引起的肝纤维化过程中基质金属蛋白酶（MMPs）和MMPs抑制剂（TIMPs）的内源性组织表达的动态变化。方法：将雄性Sprague-Dawley大鼠随机分为正常组，4天，2周，4周，9周和11周，并且在模型设计的时间分别通过灌胃向模型大鼠喂食酒精混合物。然后分离，收集它们的肝脏，分别通过免疫组织化学，酶促法和蛋白质印迹法检查MMP-2，MMP-3，MMP-9，MMP-13，TIMP-1和TIMP-2。结果：正常大鼠的MMP-2表达中等，除11周组MMP-2表达略有增加外，其余均在模型大鼠中降低。尽管表达较弱，但MMP-3具有与MMP-2类似的变化模式。 MMP-9表达在4 d和2 wk组下降，在4 wk组上升，在9 wk组再次下降，在11 wk组恢复到正常水平。 MMP-13表达在4 d和2 wk组下降，在4 wk，9 wk和11 wk组恢复到正常水平。 TIMP-1表达在4 d和2 wk组下降，但在4 wk组急剧增加，即使在模型停止2 wk后仍保持高水平。在正常大鼠中，TIMP-2表达很强。然而，它在建模开始后立即下降，然后逐渐上升，但即使在模型停止2周后仍保持低于正常大鼠的水平。结论：肝纤维化过程中MMP-2可能并不总是高表达。 MMP-13和MMP-3受到TIMP-1的严重影响。在该模型中，TIMP-1是施加于毛细血管化和正弦周围纤维化的最有力因素。 TIMP-2是对位于窦底的IV型胶原代谢最有效的调节剂。

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