摘要目的　探讨血管成形术后Ⅰ型胶原的动态演变规律及其与MMP-1和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、透射电镜加图象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表型在早期主要是增生型,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=0.65, P<0.01).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的活性比值并与VSMC表型特征有一定的联系.

abstractsObjective To investigate the dynamic changes of type Ⅰ collagen, and the activity of metalloproteinases-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) after angioplasty. Methods The restenotic model of iliac arteries of domestic microswine was established with hypercholesterol feed plus two angioplasties. Angioplastied vessels were harvested at the end of 1, 2, 3 and 6 months after the second angioplasty. Immunohistochemistry, transmission electronic microscopy and image quantitative analysis techniques were employed to study neointimal proliferation, the phenotype of vascular smooth muscle cells (VSMC) and the expression of type Ⅰ collagen, MMP-1 and TIMP-1. Results The peak of vascular neointimal proliferation was at 3 months after angioplasty. The expression of type Ⅰ collagen gradually increased from 1 to 6 months after angioplasty. For MMP-1, expression was lower in the early stage after angioplasty but increase to normal levels of control vessels at 6 months after angioplasty. Expression of TIMP-1 rapidly increased in the early phase after angioplasty, reached peak at 3 months and maintained the high level till 6 months after angioplasty. Meanwhile, the VSMC was predominantly the synthetic phenotype at the early stage and was transformed to the contractive phenotype at the late stage after angioplasty. The ratio of TIMP-1 and MMP-1 was positively related to the area of the neointima and the expression of type Ⅰ collagen respectively (P<0.01). Conclusion Type Ⅰ collagen increased gradually after angioplasty, which might be determined by the ratio of TIMP-1/MMP-1 and also related to the phenotype of VSMC.