颅内动脉瘤组织超微结构及MMP-9表达相关调控机制的研究

The study of ultrastructural and regulation mechain of MMP-9＇s overexpression in the patiens with intracranial aneurysms

目的探讨颅内动脉瘤组织超微结构及MMP-9过度表达的相关调控机制。方法观察颅内动脉瘤标本和正常脑血管的血管壁细胞外基质的形态学变化，检测脑血管壁组织内的CD68、MMP-9mRNA表达水平及c-Jun免疫活性，进行相关统计学分析。结果电镜下见颅内动脉瘤血管壁的内皮细胞、平滑肌细胞凋亡和细胞外基质（ECM）破坏，CD68在颅内动脉瘤组织内14．60±1．72／高倍视野，正常脑血管壁内未见CD68阳性表达（P〈0．01）；c-Jun免疫活性在颅内动脉瘤组织内为1．92±0.51，正常脑血管壁内为0．17±0．41（P〈0．01）；动脉瘤组织中MMP-9mRNA的表达是正常对照的10．06倍（P〈0．01）；CD68和MMP-9mRNA之间呈显著正相关（r1=0．931）；颅内动脉瘤组织内c-Jun和MMP-9mRNA之间呈显著正相关（r2=0．818）。结论颅内动脉瘤瘤壁组织中阳性表达的CD68可能通过激活c-Jun进而诱导MMP-9的大量表达破坏ECM参与颅内动脉瘤的发病机制。

Objective To investigate the uhrastructural and the regulation mechain of MMP-9＇s overexpression in the patiens with intracranial aneurysms. Method The ultrastructure of aneurysms and vessel were observed with transmission electron microscope, the expression of CD68 and c-Jun and the gene expression levels of MMP-9 mRNA in tissue samples of 15 cerebral aneurysms and 6 cases from normal brain vessel without vascular disorder were measured by immunohistochemical SP method and real time TaqRT-PCR quantify method respectively. Results The damage of endothelial cell was found in aneurysms, what＇s more, the media smooth muscle cell apoptosis was found, ECM was damaged obviously. The expression levels of CD68 and c-Jun, MMP-9mRNA were significantly upregulated in aneurysms compared with that of the normal artery（ 14.60±1.72/high multiple vision versus 0, 1.92±0.51 versus 0.17±0.41,10. 06fold. P〈0.01 respectively）. There were a significant parallel tendency between CD68, c-Jun and MMP-9mRNA respectively. Conclusions The positive expression of CD68 in intracranial aneurysm may induct a overexpression of MMP-9 through activation of CD68, and the overexpression of MMP-9 destroy ECM to take part in the pathogenesis of the intracranial aneurysm.