关键词: 慢性全脑低灌注, 白质损伤, 基质金属蛋白酶-2, 基质金属蛋白酶-7, 透射电镜, 免疫组织化学, 免疫印迹法, 大鼠

Abstract: Objective To investigate periventricular white matter change and matrix metalloproteinase-2 and 7（MMP-2 and MMP-7） expression after chronic cerebral hypoperfusion in rats. Methods Sixty healthy male Wistar rats were randomly divided into sham-operated (control) group and three model groups(20 days, 40 days and 60 days). Model of chronic cerebral hypoperfusion was induced by staging permanent ligation of the bilateral common carotid arteries in the rat. The ultrastructure change in periventricular white matter was observed with transmission electron microscopy. The activation of astrocytes was assessed with immunohistochemistry staining of glial fibrillary acidic proteinl(GFAP), and the expressions of MMP-2, 7 and myelin basic protein(MBP) were detected with immunohisitochemisty staining and Western blotting. Results Irregular myelin sheaths and degenerating myelinated axon were observed at the ultrastructural level in the corpus callosum and internal capsule of the 20 days operated rats. Obvious proliferation hypertrophy of GFAP immunopositive astrocytes were observed and the expression of GFAP gradually increased in the model groups, while the content of MBP decreased（EM>P/EM>< 0. 01）. The expressions of MMP-2 and MMP-7 were markedly elevated in the model groups（EM>P/EM>< 0. 01 or EM>P/EM>< 0. 001）. Additionally, the up-regulation of MMP-2 and MMP-7 showed a significant relation with periventricular white matter matter lesions. Conclusion Chronic cerebral hypoperfusion induces progressive periventricular white matter lesions with the upregulation of MM

Key words: Chronic cerebral hypoperfusion, White matter lesion, Matrix metalloproteinase-2, Matrix metalloproteinase-7, Transmission electron microscopy, Immunohistochemistry, Western blotting, Rat