小鼠慢性脑血流低灌注状态的行为学检测及病理学观察  

Behavioral and pathologic changes of chronic cerebral hypoperfusion in mice

作　　者：段炜[1] 郑健[1] 桂莉[1] 田洪[1] 

机构地区：[1]第三军医大学新桥医院神经内科,重庆400037

出　　处：《第三军医大学学报》2009年第9期813-817,共5页Journal of Third Military Medical University

摘　　要：目的观察小鼠慢性脑血流低灌注状态下行为学及其病理学变化。方法62只C57BL/6小鼠均分为模型组和假手术组。模型组:采用内径为0.18mm的微型弹簧圈套C57BL/6小鼠双侧颈总动脉,造成血管狭窄导致全脑血流低灌注状态;假手术组:仅暴露双侧颈总动脉,不圈套微型弹簧。在成模30d时两组各取8只小鼠,采用八臂迷宫实验检测小鼠认知功能的改变,并在成模7、14d和30d时分别处死动物,采用Kluver-Barrera染色观察神经纤维改变及免疫组化观察胶质细胞增生程度,同时用Evans Blue荧光观察血脑屏障通透性的变化。结果建模30d后模型组八臂迷宫实验工作记忆错误显著多于假手术组(P<0.05)。在成模7d时未见显著病理变化,在14、30d时观察到模型组脑白质区域神经纤维稀疏[胼胝体神经纤维损伤分级分别为(1.13±0.05)和(1.96±0.08),P<0.05],星形胶质细胞和小胶质细胞显著增生[胼胝体星型胶质细胞计数分别为(104.52±12.31)和(192.57±24.23),小胶质细胞计数分别为(98.25±15.27)和(172.36±18.29),P<0.01],EvansBlue荧光观察到脑内微血管血液成分外渗。结论慢性脑血流低灌注状态导致小鼠的认知功能下降、胼胝体等白质神经纤维稀疏及胶质细胞增生。Objective To observe behavioral characteristics and pathologic changes of chronic cerebral hypoperfusion in mice. Methods Totally 62 adult C57BL/6 mice were subjected to either sham-operation （n =31） or bilateral common carotid artery stenosis using external microcoils with an inner diameter of 0.18 mm（n =31 ）. At 30 d after the stenosis, the animals of the 2 groups （8 mice for each group） underwent behavioral test of 8-arm radial maze. In 7, 14 and 30 d, the rest mice were sacrificed for their brain tissue samples which were examined with Kluver-Barrera staining and immunohistochemical assay for markers of microglia and astroglia, glial fibrillary acidic protein （GFAP） and CD1 1b. In 14 d after the model establishment, Evans blue dye extravasation test was performed for the blood-brain barrier function. Results The model group made significantly more errors than sham-operated group in 8-arm radial maze test at 30 d after the surgery. White matter lesions occurred and the proliferation of activated mieroglia and astroglia were observed in white matter in model mice after 14 and 30 d bilateral common carotid artery stenosis. The disruption of blood-brain barrier function of model mice was indicated in the evans blue extravasation test at 14 d after bilateral common carotid artery stenosis. Conclusion Cognitive impairment, white matter lesions and glial activation are suc- cessfully induced after bilateral common carotid artery stenosis in mice model of chronic cerebral hypoperfusion.

关 键 词：慢性脑血流低灌注 脑白质疏松 认知功能障碍 小鼠 

分 类 号：R-332[医药卫生] R363