基质金属蛋白酶在人主动脉根部瘤中的表达

The expression and possible mechanisms of matrix metalloproteinase in the human aortic root aneurysm

目的:基质金属蛋白酶含量增多可能促进腹主动脉瘤、胸主动脉瘤和主动脉夹层的发展,但在主动脉根部瘤的发病过程中的作用尚不十分清楚。该研究旨在人升主动脉壁组织水平上观察MMP-2和MMP-9在正常升主动脉和主动脉根部瘤中表达的不同,以探讨基质金属蛋白酶在主动脉根部瘤的发病过程中可能的作用机制。方法:收集2014年1月至2014年6月,在北京安贞医院接受主动脉根部替换术患者的升主动脉根部组织5例及心脏移植供体正常的升主动脉根部组织5例,进行免疫组化染色,并提取蛋白,检测基质金属蛋白酶在主动脉根部瘤临床标本中的表达,并探讨基质金属蛋白酶在主动脉根部瘤发病过程中可能的作用。结果:Western-blotting结果显示:主动脉根部瘤患者的标本中的MMP-2和MMP-9的蛋白表达量显著高于正常对照组标本中的表达量,正常主动脉与主动脉根部瘤中MMP-2和MMP-9的蛋白灰度值的比值分别为[(1.0±0.1)vs.(1.9±0.2),P<0.01及(1.0±0.2)vs.(1.6±0.1),P<0.01]。这说明MMP-2和MMP-9的蛋白表达量在主动脉根部瘤患者的升主动脉壁中是升高的。免疫组化发现,与正常升主动脉壁相比较,主动脉根部瘤标本的棕黄色颗粒数量显著增多(P<0.01),可能表明MMP-2和MMP-9在主动脉根部瘤标本中的表达明显升高。结论:基质金属蛋白酶中的MMP-2和MMP-9可能是影响主动脉根部瘤形成的新的作用靶点,即MMP-2和MMP-9可能直接参与重构细胞外基质蛋白,进而促进人主动脉根部瘤的形成。

Objective： Increased matrix metalloproteinases（ MMPs） may promote the development of abdominal aortic aneurysm,thoracic aortic aneurysm and aortic dissection,but the role of MMPs in the pathogenesis of aortic root aneurysm is not yet clear. This study aimed to detect the different expression of MMP-2and MMP-9 between normal ascending aortic wall tissue and ascending aortic wall tissue of aortic root aneurysm,and thus to explore the role of MMPs in the pathogenesis of aortic root aneurysm. Methods： From Jan.2014 to Jun. 2014,aortic root tissues were collected from 5 patients who performed aortic root replacement while the normal ascending aortic root tissues from 5 donors ＇hearts during heart transplantation in Beijing Anzhen Hospital. These tissues were analyzed by immunohistochemistry. Then related proteins were extracted from the aortic root wall tissues to detect the expression of MMPs. After that,we could explore the possible role of MMPs in the pathogenesis of aortic root aneurysm. Results： Results of western-blotting showed that the expressions of MMP-2 and MMP-9 in the aortic root aneurysm tissues were significantly higher than that in thecontrol group,and the ratio of statistical analysis results were [（ 1. 0 ± 0. 1） vs.（ 1. 9 ± 0. 2）,P〈0. 01） and（ 1. 0 ± 0. 2） vs.（ 1. 6 ± 0. 1）,P〈0. 01],which suggested that MMP-2 and MMP-9 increased in patients with aortic root aneurysm. Immunohistochemistry results showed that yellow-brown particles in aortic root aneurysm specimens were heavier than that in the control group（ P〈0. 01）,which further indicated that the expressions of MMP-2 and MMP-9 increased significantly in the aortic root aneurysm tissues. Conclusion： MMP-2 and MMP-9 in the matrix metalloproteinases seem to be novel targets,which may play significant roles in the pathogenesis of aortic root aneurysm： MMP-2 and MMP-9 may directly affect the extracellular matrix proteins remodeling,contributing to the pathological change of human aortic root aneurysm.