活性金属基质蛋白酶-9的表达增高可能导致脑动静脉畸形出血风险增加的研究

Study on High Level Expression of Activated MMP-9 may Increase Hemorrhagic Risk of Cerebral Arteriovenous Malformation

目的探讨金属基质蛋白酶-9(matix metalloproteinase-9,MMP-9)在脑动静脉畸形出血机制中的作用。方法收集2010年10月至2011年3月天坛医院住院的脑动静脉畸形(arteriovenous malformation,AVM)患者及颞叶癫痫患者。根据手术切下的动静脉畸形的血管巢及癫痫手术患者术中切除的脑组织,分为脑动静脉畸形出血组(14例)、未出血组(17例)和对照组(25例)。采用Western蛋白印迹检测组织中MMP-9蛋白水平的表达。采用免疲荧光方法检测各组MMP-9的表达,明胶酶谱检测组织中有活性的MMP-2和MMP-9蛋白的表达。结果 MMP-9蛋白在未出血组中表达高于对照组和出血组(1.21±0.34 vs 0.35±0.06,P=0.0014;1.21±0.34 vs 0.32±0.08,P=0.047),出血组和对照组之间差异无显著性(0.32±0.08 vs0.35±0.06,P=0.7456)。显示MMP-9蛋白的活性明胶酶谱中,出血组和未出血组及对照组之间的差异有显著性(0.97±0.08 vs 0.40±0.09.P=0.009;0.97±0.08 vs 0.30±0.07,P=0.0034)。在出血组,有活性的MMP-2的表达同样高于未出血组和对照组,差异有显著性(1.36±0.17 vs 0.55±0.12,P=0.019;1.36±0.17 vs 0.36±0.09,P=0.006)。结论在脑动静脉畸形组织中活性MMP-9表达增高,在破裂出血的动静脉畸形中MMP-9更多转化为活性的形式出现。

Objective To investigate the role of MMP-9 in the hemorrhagic mechanism of cerebral arteriovenous malformation（AVM）. Methods Thirty-one patients with AVMs and 25 patients with epilepsy were admitted in our hospital during October 2010 to March 2011. The AVM tissue samples were divided into a ruptured group, non-ruptured group and control group. Tissue samples were obtained from the AVM nidus during surgery or from the temporal lobectomy of patients undergoing surgical treatment of epilepsy. Western blot analysis was used to measure MMP-9 in the tissues. Immunofluorescence was used to measure tissue MMP-9 expression in each group. Gelatin zymography showed the expression of activated MMP-2 and MMP-9 in the tissue. Results MMP-9 protein expression in the non-ruptured group was greater than that in the normal group and the ruptured group. （1.21±0.34 vs 0.35±0.06, P=0,0014; 1.21±0.34 vs 0.32±0.08, P=0.047）, but no difference between the ruptured and the control group（0.32±0.08 vs 0.35±0.06, P=0.7456）. Gelatin zymography showed that the activity of MMP-9 was significantly higher in the ruptured than the non-ruptured and control groups（0.97±0.08 vs 0.40±0.09, P=0.009; 0.97±0.08 vs 0.30±0.07, P=0.0034）. In the ruptured group, active MMP-2 expression was significantly higher than that in the unruptured and control group（1.36±0.17 vs 0.55±0.12,P=0.019; 1.36±0.17 vs 0.36± 0.09, P=0.006）.Conclusion MMP-9 had higher expression in the AVM tissues and more MMP-9 transformed to activated form in ruptured AVM tissues; this may lead to increase in hemorrhage risk due to AVM.