摘要
目的观察慢性全脑低灌注大鼠侧脑室旁白质改变及基质金属蛋白酶-2和7(MMP-2和MMP-7)的表达并探讨其意义。方法 Wistar雄性大鼠60只,随机分为假手术组和模型组(20d组、40d组、60d组)共4组。模型组行双侧颈总动脉分期永久结扎术制备慢性全脑低灌注模型。透射电镜观察胼胝体和内囊超微结构变化;胶质纤维酸性蛋白(GFAP)免疫组织化学染色观察星形胶质细胞变化;免疫印迹法检测髓鞘碱性蛋白(MBP)含量变化;免疫组织化学染色和免疫印迹法观察和检测MMP-2和7表达变化。结果电镜观察可见模型20d组侧脑室旁白质有髓纤维髓鞘发生变形、板层结构疏松、崩溃等脱髓鞘改变,血管周围有明显水肿现象,而假手术组未见明显变化。各模型组见星形细胞胞体肥大、突触增粗、数量增多,随低灌注时间延长GFAP表达增多,而MBP减少,较假手术组差异均有明显统计学意义(P<0.01)。各模型组MMP-2和MMP-7表达均较假手术组增多(P<0.01或P<0.001),MMP-2和MMP-7表达与侧脑室旁白质损伤呈明显正相关。结论大鼠慢性全脑低灌注引起持续性的侧脑室旁白质缺血性损伤,MMP-2和MMP-7表达上调可能参与白质损伤的进展。
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 ultrastrueture change in periventricular white matter was observed with transmission electron microscopy. The activation of astroeytes 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 uhrastruetural 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 （P 〈 0. 01 ）. The expressions of MMP-2 and MMP-7 were markedly elevated in the model groups（P 〈 0. 01 or P 〈 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 MMP-2 and MMP-7 whieh may involve in the pathological process of white matter lesions.
出处
《解剖学报》
CAS
CSCD
北大核心
2010年第5期654-659,共6页
Acta Anatomica Sinica
基金
福建省青年科技人才创新基金(3031713)资助
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
Chronic cerebral hypoperfusion
White matter lesion
Matrix metalloproteinase-2
Matrix metalloproteinase-7
Transmission electron microscopy
Immunohistochemistry
Western blotting
Rat
作者简介
詹增土（1983-），男（汉族），福建省永泰县人，在读硕士研究生。
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