摘要目的 观察急性升主动脉夹层(AAD)基质金属蛋白酶-9(MMP-9)表达和中膜血管平滑肌细胞(VSMC)病变.方法 35例急性AAD病例为研究对象(病变组),21例同期心脏移植供心者的升主动脉为对照组,应用透射电镜、免疫组化等方法,观察病变主动脉壁VSMC和基质变化;检测MMP-9在病变组和对照组血管壁中的表达;并将病变组按瘤径分为<55 mm和瘤径≥55 mm两个亚组,比较组间MMP-9表达情况并探讨吸烟、高血压病、瘤径等因素对MMP-9表达的影响.结果 病变组中膜VSMC合成功能旺盛,VSMC密度减小,弹性纤维崩解,管壁纤维化;对照组主动脉壁未见异常.对照组主动脉壁几乎不表达MMP-9;病变组中膜VSMC大量表达MMP-9(P<0.001),且其与瘤径(P<0.05)和合并高血压病(P<0.01)呈正相关,两亚组中,大瘤径亚组MMP-9表达显著(P<0.05).结论 血压升高增强升主动脉VSMC分泌功能,促进MMP-9表达,破坏弹性蛋白等基质成分,引起主动脉壁纤维化,管壁抗张强度下降,致局部主动脉内膜撕裂发生急性AAD.

abstractsObjective Ascending aortic dissection(AAD),for which the pathogenesis remains unknown,is life-threatening.Matrix metalloproteinase-9(MMP-9)and the pathological changes of vascular smooth muscle cells(VSMCs)have been reported to have roles the pathogenesis.The study examined the expression of matrix metalloproteinase-9(MMP-9)and the pathological changes of,VSMCs in patients with AAD.Methods AAD samples were taken from 35 patients(disease group)in acute phase during aortic replacement operation for AAD and control samples were corresponding part of ascending aorta(control group,n=21)collected from the donor hearts for transplantation.Transmission electron microscepe,hematoxylin-eosin(H-E)staining.Mallory staining were used for observing the pathological changes of VSMCs and matrix in the affected aortic wall.The immunohistochemicai staining of MMP-9 was carried out in both groups and semi-quantified by staining intensity analysis.The affected patients were further grouped according to the diameter of dissected aorta as with a AAD of <55 mm or with a AAD of≥55 mm.The associations of clinical factors,such as smoking status,hypertensive disease and aneurysm diameter,with the expression of MMP-9 were analyzed.Results Increased synthetic function of VSMCs with decreased density,disrupted elastic fibers and fibrosis in the dissected aortic wall were observed in the disease group,but not in the control group.MMP-9 was scarcely expressed in the aortic wall of the patients in the control group,though it was notably expressed in the VSMCs of disease group.Both subgroups presented more MMP-9 than the control group(both P<0.001).In the disease group,sub-group with a AAD diameter of ≥55 mm presented more MMP-9 than that with a diameter of <55 mm(P<0.05).MMP-9 expression was positively correlated with a history of hypertension(P<0.01)or a great aneurysm diameter(P<0.05).MMP-9 expression was not associated with age,smoking status or other clinical factors.Conclusion Increased secretion of VSMCs and the expression of MMP-9 induced by elevated blood pressure may lead to the destruction of matrix proteins.The resulting fibrosis of the aortic wall would decrease the tensile strength of the wall.When the fibrotic aortic wall dilated further,the increased expression of MMP-9 would aggravate the damage to the wall.It can be speculated that acute AAD would occur as a result of partial tearing of the aortic intima.