大鼠自体移植静脉中转化生长因子β1和基质金属蛋白酶1及其抑制剂的基因表达
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国家自然科学基金资助(30371401)


Gene Expression of Transforming Growth Factor-β1, Matrix Metalloprotein-Ase-1, and Matrix Metalloproteinase Tissue Inhibitor-1 in Autogenous Vein Grafts in Rats
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    摘要:

    目的观察转化生长因子β1和基质金属蛋白酶1及其抑制剂在大鼠自体移植静脉中的动态表达,探讨它们与移植静脉内膜增生之间的关系。方法建立大鼠自体静脉移植模型,随机分成3、7、14和28天组。行苏木素—伊红及Verhoffe染色,计算机图像分析系统测量不同时间点的内膜和血管壁厚度。采用Western印迹和逆转录—聚合酶链反应测定转化生长因子β1、基质金属蛋白酶1及基质金属蛋白酶组织抑制剂1的蛋白及mRNA表达。结果术后7天内膜明显增厚,与对照组比较有统计学意义(p<0.05),术后14天内膜增生达到高峰。转化生长因子β1蛋白表达在术后第3天开始增加,第7天达到高峰,第28天回到基线水平。3天和7天组基质金属蛋白酶1的蛋白水平与对照组比较没有明显差别,14和28天组比对照组明显减少。基质金属蛋白酶组织抑制剂1的蛋白表达在第14和28天明显增加。三者mRNA水平的变化趋势与蛋白表达结果相似。结论转化生长因子β1通过破坏基质金属蛋白酶1与基质金属蛋白酶组织抑制剂1之间的平衡,从而使细胞外基质过量堆积,是内膜增生和血管狭窄形成的机制之一。

    Abstract:

    Aim To investigate the dynamic expression of transforming growth factor-β1(TGF-β1), matrix metalloproteinase-1(MMP-1), and matrix metalloprotinase tissue inhibitor-1 (TIMP-1), and their relations with intimal hyperplasia in autogenous vein grafts in rats. Methods Animal models were constructed. The vein grafts were collected on day 3, day 7, day 14, and day 28 after operations. HE and Verhoffe staining and computer image analysis system were used to explore the thickness changes of intima and wall at different time points. Western blot and reverse transcription polymerase chain reaction(RT-PCR) were used to detect the protein and mRNA level of TGF-β1, MMP-1, and TIMP-1 in vein grafts and controls. Results Histomorphological analysis showed that the intimal thickness increased remarkably on day 7 after operation compared with control(p<0.05), and reached a peak on day 14. Western blot revealed that protein level of TGF-β1 increased on day 3, peaked on day 7 and returned to the baseline on day 28. MMP-1 protein was not significantly different with control on day 3 and 7 respectively, but decreased significantly on day 14 and 28. TIMP-1 protein increased significantly on day 14 and 28. Their mRNA level had similar tendency with the results of Western blot. Conclusions TGF-β1 decreased MMP-1 activity by increasing TIMP-1 expression, and facilitate the excessive accumulation of ECM so as to cause intimal hyperplasia and stenosis.

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孙达欣,张强,郎晓讴,刘明辉.大鼠自体移植静脉中转化生长因子β1和基质金属蛋白酶1及其抑制剂的基因表达[J].中国动脉硬化杂志,2005,13(3):275~278.

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  • 收稿日期:2004-08-25
  • 最后修改日期:2005-01-24
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