基质金属蛋白酶9在腹主动脉瘤体组织中的高度表达及其致病作用(英文)

High expression of matrix metalloproteinase-9 and its role in the pathogenesis of human abdominal aortic aneurysms

背景:人腹主动脉瘤的发病机制十分复杂,目前尚未完全明了,基质金属蛋白酶9在腹主动脉瘤形成与发展过程中可能具有促进作用。目的:通过检测基质金属蛋白酶9在人腹主动脉瘤组织中的定位表达,评价基质金属蛋白酶9在腹主动脉瘤发病机制中的作用及临床意义。设计:随机对照、重复测量设计。单位:德国科隆大学医院血管外科中心。对象:组织标本选择2002-05/2003-02德国科隆大学医院血管外科中心手术治疗的腹主动脉瘤患者20例,男18例,女2例;年龄56～81岁;随机选择下肢动脉硬化闭塞症血管旁路手术患者15例及其他非血管手术患者10例为对照。方法:同样条件下切取上述患者腹主动脉瘤瘤体组织、下肢动脉硬化闭塞症硬化动脉管壁和正常动脉管壁组织。采用免疫组织化学技术,检测了基质金属蛋白酶9在20例腹主动脉瘤瘤体组织中的定位表达,并与15例下肢动脉硬化闭塞性疾病的病变管壁、10例非血管疾病(正常动脉)管壁组织中的基质金属蛋白酶-组织学表达进行对照研究。主要观察指标:基质金属蛋白酶9在3种不同动脉血管条件下的组织定位表达结果及表达水平。结果:①腹主动脉瘤动脉壁中富含大量基质金属蛋白酶9颗粒,其阳性表达率达95%(19/20)。②正常动脉管壁组织未检测到基质金属蛋白酶9的表达;下肢动脉硬化病变血管壁内可见散在分布的基质金属蛋白酶9阳性颗粒,其阳性表达率为26.7%(4/15)。③与正常动脉管壁和下肢动脉硬化血管壁相比较,基质金属蛋白酶9在腹主动脉瘤瘤体组织中的表达具有显著性差异(P<0.01)。结论:腹主动脉瘤体组织中基质金属蛋白酶9的高表达,促进主动脉中层细胞外基质崩解进而导致动脉弹性下降、动脉扩张及进一步的瘤体形成,在腹主动脉瘤的发病机制中具有重要作用。

BACKGROUND： The pathogenesis of human abdominal aortic aneurysms （AAAs） is sophisticated and has not been well understood so far, matrix metalloproteinase-9 （MMP-9） may play a role in the formation and development of AAAs. OBJECTIVE： To evaluate the effects and clinical significance of MMP-9 in the pathogenesis of AAAs by localizing the expression of MMP-9 within human aneurysmal tissues. DESIGN： A design with randomized control and repeated measurement. SETTING： Center for Vascular Surgery, Affiliated Hospital of University of Cologne. MATERIALS： Tissue samples were from 20 patients with AAAs who received the treatment in the Center for Vascular Surgery, Affiliated Hospital of University of Cologne between May 2002 and February 2003. They were 18 male and 2 female with age of 56 to 81 years; 15 patients with atherosclerosis occluded diseases （AODs） of low extremities who underwent vascular by-pass operation were randomly chosen and other 10 patients who did not underwent vascular operation were chosen as control. METHODS： Aneurysmal tissue of patients with AAAs, arterial canal tissue of patients with arteriosclerotic occlusion of lower extremities and normal arterial canal tissue were cut off under the same condition. The locational expression of MMP-9 of abdominal aortic aneurismal tissue of 20 patients was detected with immunohistochemical technique. Arterial samples from the other 15 cases with AODs and 10 cases with normal arteries were also obtained to serve as control. MAIN OUTCOME MEASURES： Tissue locational expression of MMP-9 in these three different diseases and their locational expression level. RESULTS： A quantity of positive granules which appeared within the aortic media showed the strong expression of MMP-9 in the AAAs, with the positive rate reaching 95%（19/20）, while no expression of MMP-9 was observed in the normal artery. However, the scattered distributed positive granules were seen within the arterial wall of 4 cases out of 15 AODs, implying the weak positive expression of MMP-9 in this disease with the positive rate of 26.7%（4/15）. There was a significant difference of the expression of MMP-9 in the arterial wall between the AAAs and AODs（P 〈 0.01）. CONCLUSION： The high expression of MMP-9 in the aortic media faciliatates the degradation of collagen and elastic fibers and subsequent dilation of the aortic artery, which may play an important role in the pathogenesis of AAAs.