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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 the behavior and pathological changes of chronic cerebral hypoperfusion in mice. Methods Sixty two C57BL / 6 mice were divided into model group and sham operation group. Model group: Bilateral common carotid arteries of C57BL / 6 mice were occluded with a mini spring coil with an inner diameter of 0.18 mm, resulting in stenosis of blood vessels leading to hypoperfusion of whole cerebral blood flow. Sham-operated group: bilateral common carotid arteries were exposed only, spring. At the 30th day after injection, eight mice in each group were sacrificed and the changes of cognitive function in mice were detected by eight-arm maze test. Animals were sacrificed on the 7th, 14th, and 30th day after modeling. Kluver-Barrera staining was used to observe the changes of nerve fibers The changes of glial cell proliferation were observed by immunohistochemistry, and the permeability of blood-brain barrier was observed with Evans Blue fluorescence. Results After modeling for 30 days, the memory error of the eight-arm maze test in the model group was significantly more than that in the sham operation group (P <0.05). There were no significant pathological changes at 7 days after operation, and the nerve fibers in the white matter region of the model group were observed sparse at 14 and 30 days (1.13 ± 0.05 and 1.96 ± 0.08, P <0.05, respectively) , Astrocytes and microglial cells were significantly proliferated (astrocyte count of corpus callosum were (104.52 ± 12.31) and (192.57 ± 24.23, respectively, microglial counts were (98.25 ± 15.27) and (172.36 ± 18.29), P <0.01], extravasation of microvascular blood components in the brain was observed with EvansBlue fluorescence. Conclusion Chronic cerebral hypoperfusion results in decreased cognitive function, sparse corpus callosum and glial proliferation.