MD患者颈内动脉组织学及ICAM—1、MMP-9的表达变化  

Histological changes and ICAM-1 and TMMP-9 expressions in the internal carotid arteries of patients with moyamoya disease

作　　者：韩利江[1] 赵继宗[1] 孙异临[2] 赵元立[1] 张东[1] 袁葛[1] 季楠[1] 田永吉[1] 任同[1] 

机构地区：[1]首都医科大学附属北京天坛医院神经外科,北京100050 [2]中国医学科学院神经科学研究所,北京100050

出　　处：《中华神经医学杂志》2009年第9期889-892,共4页Chinese Journal of Neuromedicine

摘　　要：目的观察Moyamoya病（MD）患者颈内动脉组织学、钙依赖性细胞粘附分子（ICAM—11、Ⅳ型胶原酶（MMP-2，MMP-9）及其组织抑制因子（TIMP-1，TIMP-2）mRNA的表达变化，以探讨MD的发病机制。方法尸解取MD患者病变侧颈内动脉颅内段，应用HE、Wergeit染色检测其组织学改变，透射电镜观察其超微结构，应用免疫组化和原位杂交分别检测颈内动脉ICAM-1和MMP-2、MMP-9、TIMP-1、TIMP-2mRNA的表达，同时设非血管病死亡的患者颈内动脉做对照。结果HE染色显示MD患者颈内动脉变细，存在不同程度的管腔狭窄、闭塞及钙化；Wergeit染色可见病变侧颈内动脉内膜纤维样增厚，内弹力层变薄、断裂，中膜平滑肌细胞变性，外弹力层厚薄不均．外膜变薄．局部剥落：透射电镜显示内膜增厚处平滑肌细胞增生，部分中膜肌细胞空泡变性，内质网扩张，线粒体肿胀或浓缩；免疫组化显示MD患者颈内动脉各层ICAM-1阳性标记多于对照患者．且以内膜处为主：原位杂交检测发现MD患者病变侧颈内动脉内膜、中膜和外膜存在MMP-9mRNA的阳性杂交信号，以内弹力层处密集。结论ICAM-1、MMP-9的高表达可能是导致颈内动脉弹力层、外膜破坏及管壁塌陷、狭窄、甚至完全闭塞的原因之一，与MD的形成有关。Objective To observe the histopathological and ultrastructural changes, alterations in the expressions of type IV collagenases （MMP-2 and MMP-9）, the tissue inhibitors （TIMP-1 and TIMP-2） and intercellular adhesion molecule-1 （ICAM-1） in the internal carotid arteries （ICAs） of patients with moyamoya disease （MD）, and explore the pathogencsis of MD. Methods The bilateral ICAs were obtained during autopsy from two MD patients. HE staining and Weigert staining was used for histological observation, and transmission electron microscopy was employed to observe the ultrastructure of the ICAs. The expression of ICAM-1 in the ICAs was detected using immunohistocbemical staining, and the mRNA exprcssinns ofMMP-2, MMP-9, TIMP-1 and TIMP-2 were assayed using in situ hybridization. The ICA specimens from two patients died from non-vascular diseases were used as the control. Results HE staining revealed thinning of the ICAs of the MD patients with luminal stenosis, obstruction and calcification. Weigert staining identified fibrous thickening of the intima, thinning and fragmentation of the elastica interna （EI） and elastiea cxterna （EE）, degeneration of the smooth muscle cells in the media, and thinning and local exfoliation of the adventitia. Immunohistochemistry showed ICAM-1 expression in the ICAs of both MD and control patients, but the MD patients exhibited a stronger ICAM-1 positivity in the ICAs localized primarily in the tunica intima.The ICA wall was positive for MMP-9 mRNA expression, which was especially intense in the elastica intema, as shown by in situ hybridization. Conslusions The high expression of MMP-9 and ICAM-1, destruction of the elastic layer and adventitia, and collapse of the vascular wall result in luminal stenosis or even obstruction of the ICAs, which can be associated with the occurrence of MD.

关 键 词：MOYAMOYA病 颈内动脉 钙依赖性细胞黏附分子 基质金属蛋白酶一9 

分 类 号：R686[医药卫生—骨科学]