MMP-1、TIMP-1及TGF-β1在风湿性心脏病瓣膜组织中的表达及意义

Significance and Expressions of MMP-1,TIMP-1 and TGF-β1 in Valve Tissues of Rheumatic Heart Disease

目的探讨基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶组织抑制剂-1(TIMP-1)及转化生长因子-β1(TGF-β1)在风湿性心脏病(RHD)瓣膜组织中的表达及意义。方法采用Western blot及RT-PCR法检测RHD瓣膜组织(实验组,n=30)及无RHD瓣膜组织(对照组,n=15)中MMP-1、TIMP-1及TGF-β1蛋白与mRNA的表达,碱水解法检测胶原代谢情况,Masson法进行胶原纤维染色并检测胶原容积分数(CVF)。分析MMP-1、TIMP-1及TGF-β1与CVF的相关性。结果 MMP-1及TGF-β1蛋白和mRNA在实验组中的表达高于对照组,而TIMP-1蛋白和mRNA在实验组中的表达低于对照组,差异有统计学意义(P<0.05)。实验组胶原含量及CVF均高于对照组(P<0.05)。相关性分析显示,MMP-1与TGF-β1呈正相关,TIMP-1与TGF-β1呈负相关,MMP-1及TGF-β1与CVF呈正相关,TIMP-1与CVF呈负相关。结论 MMP-1、TGF-β1和TIMP-1参与了RHD瓣膜病变的纤维化进展。

Objective To explore expressions of matrix metalloproteinase-1 （MMP-1）, tissue inhibitor of metalloproteinases-1 （TIMP-1） and transforming growth factor-β1 （TGF-β1） in valve tissue of rheumatic heart disease （RHD）, and to analyzed their roles in RHD. Methods The expressions of MMP-1, TIMP-1 and TGF-β1 proteins and mRNAs were tested by Western blot and RT-PCR methods in valve tissues in participants with （experimental group, n=30） and without RHD （control group, n=15）. Collagen fibers were detected by Masson staining, and collagen volume fraction （CVF） was caculated. The correlations of CVF and the expressions of MMP-1, TIMP-1 and TGF-β1 were analyzed. Results The collagen fibers, CVF, and the protein and mRNA expressions of MMP-1 and TGF-β1 in experimental group were higher than those in control group, while the protein and mRNA expressions of TIMP-1 in experimental group were lower than those in control group. The expression of TIMP-1 was negatively correlated with TGF-β1 and CVF in valve tissues, while MMP-1 was positively correlated with them. The expression of TGF-β1 was positively correlated with CVF in valve tissues. Conclusion MMP-1, TIMP-1 and TGF-β1 contribute to the progression of fibrosis in RHD.