基质金属蛋白酶-2、-8和血管内皮生长因子在人颈动脉粥样硬化不稳定斑块的定位共表达

Localization coexpression of matrix metalloproteinase-2, -8 and vascular endothelial growth factor in unstable human carotid atherosclerosis plaques

目的探讨基质金属蛋白酶（MMP）-2、18和血管内皮生长因子（VEGF）在人颈动脉粥样硬化不稳定斑块中与平滑肌细胞、内皮细胞以及炎细胞的定位共表达特点。方法应用HE染色对手术切除的6例动脉粥样硬化（AS）患者不稳定斑块标本进行组织学观察、筛选，然后利用免疫荧光双标技术和激光共聚焦显微镜观察MMP-2、-8和VEGF在人不稳定斑块上的定位共表达情况。结果所有标本均有AS斑块的组织学特征，且均为Ⅳ型以上的不稳定性斑块；MMP-2在单核细胞浸润的斑块纤维帽平滑肌细胞和肩部单核细胞中表达最为显著，在肩部和脂质坏死区边缘增生微血管内皮细胞中也有较多表达；MMP-8表达最多见于纤维帽和脂质核心内的单核细胞中，其次共表达在纤维帽的平滑肌细胞中；VEGF在肩部增生的微血管内皮细胞中表达最为明显，由平滑肌细胞构成的纤维帽和有较多单核细胞浸润的脂质坏死区边缘也是VEGF的高表达区域。结论MMP-2、-8和VEGF可以与人不稳定斑块中的单核细胞、平滑肌细胞和内皮细胞明显共表达，表达区域主要集中在单核细胞浸润明显的斑块纤维帽、肩部以及脂质坏死区边缘新生微血管周围。

Objective To investigate the localization coexpression in situ of matrix metalloproteinase（ MMP）-2, -8 and vascular endothelial growth factor （VEGF） in human atherosclerotic unstable plaques with monocytes, smooth muscle cells （SMCs） and endothelial cells （ECs）. Methods The histopathologic changes of unstable human atherosclerotic plaques were observed by hematoxylin and eosin （HE） staining, and the localization coexpression of MMP-2, MMP-8 and VEGF in the unstable human atherosclerotic plaques were observed by double fluorescent immunochemistry technology and confocal microscopy. Results The human atherosclerotic plaques in 6 cases had typical histopathologic instability, which was classified as super-Ⅳ type unstable plaques. The MMP-2 coexpression was the most obvious in the smooth muscle cells of fibrous cap infiltrated by monocyts, and in the monocytes of shoulder of plaques, and more expression of MMP-2 in the microvascular endothelial cells at the edge of shoulder and lipid necrosis; MMP-8 coexpressed obviously with the monocytes in the fibrous cap and lipid cores of plaques, and next to coexpressing in the smooth muscle cells of fibrous cap,while coexpression in endothelial cells was very little; VEGF coexpression was significant in the proliferative microvascular endothelial cells of plaques ; The fibrous cap,which consisted of the smooth muscle cells mainly, and the edge of lipid necrosis infiltrated by more monocyts,were over-expression areas of VEGF. Conclusions MMP-2, -8 and VEGF can coexpress with monocytes,SMCs and ECs in unstable plaques, and the major expression areas are in the fibrous cap, shoulder and micro-vessel at the edge of lipid necrosis, which are infiltrated by monocytes. Moreover, the outer membrane of vessel is involved in the pathogenesis of atherosclerosis.