TGFβ1、MMP-8及其抑制剂TIMP-1在心肌重塑中的动态表达Dynamic Expression of Transforming Growth Factor β1(TGFβ1),Metalloproteinase(MMP-8) and Tissue Inhibitor of Metalloproteinase(TIMP-1) in Myocardial Remodeling
方丽,杨婷,张晓林,杨国雄,杨勤
FANG Li,YANG Ting,ZHANG Xiaolin,YANG Guoxiong,YANG Qin(Department of Pathophysiology
摘要(Abstract):
目的:探讨基质金属蛋白酶(MMP-8)及其生理性抑制剂TIMP-1和转化生长因子β1(TGFβ1)在大鼠压力负荷性心肌重塑中的动态表达及作用。方法:环扎成年Wistar大鼠腹主动脉使之缩窄,造成左心室压力负荷引起心肌重塑。观察和比较术后2、4、8、12周及假手术组大鼠左心室肌重量指数,Masson染色后比较心肌胶原含量,免疫组织化学SABC法及蛋白免疫印迹方法观察MMP-8、TIMP-1、TGFβ1蛋白表达。结果:腹主动脉缩窄术后各组大鼠发生左室重塑和纤维化,左心室肌重量指数、胶原含量及TGFβ1蛋白表达均明显高于假手术组;术后2、4、8周MMP-8表达均高于假手术组,但12周时降至假手术组水平;TIMP-1仅在术后2周有一过性增高。结论:TGFβ1表达增多、MMP-8/TIMP-1表达相对上调可能参与了大鼠压力负荷性心肌重塑的发生和发展。
Objective: To study the expression and the effects of metalloproteinase(MMP-8),tissue inhibitor of metalloproteinase(TIMP-1) and transforming growth factor β1(TGFβ1) in pressure overload rats.Methods: Myocardial remodeling model of adult Wistar rats was established by coarctating of abdominal aorta and creating pressure load in left ventricular to cause myocardial remodeling.Expression of MMP-8,TIMP-1,and TGFβ1,and myocardial remodeling index were evaluated in the 2nd,4th,8th and 12th weeks after operation and sham operation.Collagen contents were measured with Masson stained sections of cardiac muscle.Expression of MMP-8,TIMP-1,and TGFβ1was tested with immunohistochemistry SABC method and protein immunoblotting.Results: Myocardial remodeling and fibrosis predominantly occurred in left ventricle of rats in model groups.The left ventricular hypertrophic index,expression of collagen and protein of TGFβ1 were higher in rats of model groups than in rats of sham operation group(P<0.01).Expression of protein of MMP-8 elevated in the 2nd,4th and 8th weeks in rats of model groups,which was higher than that in sham operation group,and,then,decreased to the level of sham operation group in the 12th week(P<0.01).The expression of TIMP-1 elevated only in the 2nd week after operation(P<0.01).Conclusion: The expression elevation of TGFβ1 and MMP-8/TIMP-1 might relate with myocardial remodeling in pressure overload rats.
关键词(KeyWords):
心肌;心肌缺血;基质金属蛋白酶;金属蛋白酶1组织抑制剂;转化生长因子β
myocardium;myocardial ischemia;matrix metalloproteinases;tissue-inhibitor of metalloproteinase-1;transforming growth factor beta
基金项目(Foundation):
作者(Author):
方丽,杨婷,张晓林,杨国雄,杨勤
FANG Li,YANG Ting,ZHANG Xiaolin,YANG Guoxiong,YANG Qin(Department of Pathophysiology
DOI: 10.19367/j.cnki.1000-2707.2007.02.015
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文章评论(Comment):
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- 心肌
- 心肌缺血
- 基质金属蛋白酶
- 金属蛋白酶1组织抑制剂
- 转化生长因子β
myocardium - myocardial ischemia
- matrix metalloproteinases
- tissue-inhibitor of metalloproteinase-1
- transforming growth factor beta