血管成形术后Ⅰ型胶原和金属蛋白酶-1及其组织型抑制剂的动态演变规律

Relationship between type Ⅰ collagen, metalloproteinases-1 and tissue inhibitor of metalloproteinases-1 after angioplasty

目的 :探讨血管成形术后Ⅰ型胶原的动态演变规律及其与金属蛋白酶 1(MMP 1)和金属蛋白酶的组织型抑制剂 (TIMP 1)的关系。方法 :采用小型猪髂动脉再狭窄动物模型 ,分别在血管成形术后 1、2、3和 6个月取材 ,用免疫组化、透射电镜加图像分析技术观察血管内膜增生、平滑肌细胞 (VSMC)表型特征、Ⅰ型胶原、MMP 1和TIMP 1的表达情况。结果 :血管内膜增生及影像学狭窄在成形术后 3个月达高峰 ,Ⅰ型胶原的表达水平在成形术后逐渐增高 ,MMP 1的表达水平在血管成形术后早期较低 ,至 6个月时达正常血管水平 ,而TIMP 1在血管成形术后早期即明显增高 ,在 3个月内达高峰 ,6个月时仍稳定在较高水平 ;VSMC表型在早期主要是合成型 ,而后期以收缩型为主 ;TIMP 1/MMP 1的比值与新生内膜面积及Ⅰ型胶原的表达水平均呈显著正相关 (r=0 .6 5 ,P <0 .0 1)。结论 :血管成形术后细胞外Ⅰ型胶原随着时间的推移而逐渐增加 ,Ⅰ型胶原的动态演变主要取决于TIMP 1/MMP 1的活性比值 。

Objective:This study is aimed to investigate the dynamic changes of type I collagen, the relationship between type I collagen, the activities of metalloproteinases 1(MMP 1) and tissue inhibitor of metalloproteinases 1(TIMP 1) after angioplasty.Methods:The iliac restenotic model of domestic microswine was established with hypercholesterol feed plus twice angioplasties. The angioplastied vessels were harvested at the end of the 1st, 2 ed, 3 ed and 6 th month after the second angioplasty. Immunohistochemistry,transmission electronic microscopy and image quantitative analysis technique were employed to study neointimal proliferation, phenotype of VSMC, the expressions of type I collagen, MMP 1 and TIMP 1.Results:The peak of vascular neointimal proliferating arrives in 3 months after angioplasty. The expression of type I collagen was gradually increasing from 1 to 6 months after angioplasty. For MMP 1, the expression was lower in the early stage after angioplasty but increased to the normal level of control vessels at the 6th month after angioplasty. But for TIMP 1, the expression was rapidly increasing in the early stage after angioplasty, reached the peak at the 3 th month and then maintained the high level till the 6th month after angioplasty. Meanwhile the VSMC was predominantly synthetic phenotype at the early stage and transformed to contractive phenotype at the late stage after angioplasty. Ratio of TIMP 1 and MMP 1 were positively related with the area of neointimal and the expression of type I collagen respectively (P< 0.01 ).Conclusion:Type I collagen increased gradually after angioplasty and was related with the ratio of TIMP 1/MMP 1 activities and the phenotype of VSMC.