VEGF、MMP-9在人脑胶质瘤中的表达及其意义

Expressions of VEGF and MMP-9 in human gliomas and their meanings

目的探讨血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)在人脑胶质瘤中的表达及其与血管生成、瘤周水肿(PTBE)和肿瘤恶性程度的关系。方法采用免疫组化方法分别检测30例经手术和病理证实的脑胶质瘤瘤体和瘤周水肿区中VEGF、MMP-9的表达;通过计数微血管密度(MVD)来评估血管生成情况;根据CT和MRI的结果测定水肿指数;同时用透射电镜对瘤体区及瘤周水肿区的超微结构进行观察。6例来自颅脑损伤病人的正常脑组织作为对照。结果随着肿瘤级别增加MVD逐渐升高,在高级别胶质瘤体中MVD显著高于瘤周(P<0.01);VEGF、MMP-9表达与胶质瘤中的MVD均呈显著正相关(P<0.01),且两者与胶质瘤的水肿指数(EI)也均呈显著正相关(P<0.01);高级别胶质瘤的EI显著高于低级别胶质瘤(Ⅰ级、Ⅱ级)(P<0.05)。电镜下水肿明显者微血管内皮细胞胞浆内有较多小泡囊状细胞器和基底膜中有较多虫蚀样空洞等。结论 VEGF、MMP-9可能共同参与了脑胶质瘤血管生成和脑水肿的发生,并促进肿瘤的侵袭性生长。

Objective To investigate the expressions of vascular endothelial growth factor（VEGF）and matrix metalloproteinase-9（MMP-9）in human gliomas and their relationship with angiogenesis,peritumorous brain edema and the malignant degree of glioma.Methods Expressions of VEGF and MMP-9 in 30 specimens of gliomas tissues proved by surgery and pathological examination and 23 specimens of peritumorous tissues of the gliomas were determined by immunohistochemical technique.The microvessel density（MVD）in the above-mentioned specimens was determined by the technique of immunohistochemical staining of vascular endothelial cells labelled with CD34 antibody.The edema index（EI）was determined buy CT and MRI.The ultrastructures of both the tumor and peritumorous edema brain tissues were observed under an electron microscope.Six specimens of normal brain tissues derived from the patients with brain injury served as control.Results MVD,which was significantly higher in the gradesⅢ-Ⅳgliomas than that in the gradesⅠ-Ⅱgliomas（P0.01）,was significantly higher in the tumorous body tissues of than that in the peritumorous edema brain tissues of gradesⅢ-Ⅳgliomas（P0.05）.In the gliomas the expression levels of VEGF and MMP-9 were positively related to MVD（P0.01）,which was positively related to EI（P0.01）.EI in gradesⅢ-Ⅳgliomas was significantly higher than that in gradesⅠ-Ⅱgliomas（P0.01）.In the gliomas and peritumorous tissues with significant edema there were many vesicular vacuolar organellae in the endothelial cytoplasm and wormhole-like caverns of irregular size in the basilar membranes.Conclusions It is suggested that VEGF and MMP-9,which play the important roles in the angiogenesis of the gliomas and the pathogenesis of peritumorous edema,may promote the invasive growth of the gliomas.