颅内动脉瘤的MMP-9及超微结构研究

MMP-9 and ultrastructural study of intracranial aneurysms

目的探讨基质金属蛋白酶9(MMP-9)对脑血管壁细胞外基质(ECM)破坏在颅内动脉瘤发病机制中的作用。方法对15例颅内动脉瘤标本和6例非脑血管病病人的正常脑血管,应用实时荧光定量PCR检测脑血管壁组织内MMP-9mRNA的基因表达水平,并通过电镜观察颅内动脉瘤病人血管壁细胞及ECM的形态学变化。结果动脉瘤壁组织中MMP-9mRNA的表达是正常脑血管的10.06倍(P<0.01)。电镜下见动脉瘤壁内皮细胞损伤,中层平滑肌细胞数目明显减少并呈凋亡状态,ECM严重破坏;而正常脑血管壁细胞及基质纤维清晰可见,结构完整。结论颅内动脉瘤壁组织中MMP-9的基因表达水平显著升高,并可能通过破坏ECM和诱导平滑肌凋亡参与颅内动脉瘤的发病机制。

Objective To study role of matrix metalloproteinase 9 （MMP-9） destroying the extracellular matrix （ECM） in the pathogenesis of intracranial aneurysms. Methods The gene expression levels of MMP-9 mRNA in tissue samples of 15 intracranial aneurysms and 6 normal brain vessels without vascular disorder were measured by quantitative real-time fluorescence PCR, and the ultrastructures of the aneurysms and vessels were observed with transmission electron microscope. Results The expression level of MMP-9 mRNA was more significantly up-regulated in aneurysms compared with in the normal artery （10.06 fold, P 〈 0.01）. Thedamage of endothelial cells was found in the aneurysms, and the number of medial smooth muscle cell significantly decreased and cell apoptosis was found. ECM was damaged seriously, while vessel wall cells and matrix fibers were visible and the structure was normal in control group. Conclusion The expression level of MMP-9 mRNA is significantly up-regulated in aneurysms, which may destroy ECM and induce medial smooth muscle cell apoptosis, thus taking part in the aneurismal pathogenesis.