大鼠急性脑缺血再灌注后血脑屏障的变化

Blood-brain barrier changes after acute cerebral ischemia reperfusion in rats

目的 研究大鼠急性脑缺血再灌注的血脑屏障变化以及MRI表现。方法 44 只SD大鼠随机分为4 组,采用大鼠线栓法建立急性脑缺血再灌注模型,A组、C组脑缺血2 h, B组、D组缺血6 h,A组、B组中每组10 只分别于灌注前、再灌注后2 h和24 h行MRI检查,4只大鼠行组织学检查。C组、D组每组12只,分别于再灌注后2 h和24 h观察脑组织中伊文氏蓝染色情况并测量其含量。结果 A、B两组再灌注前均无强化表现,再灌注后2 hA组10例中4例出现斑片状强化,B组10例均出现大片明显强化(P<0.05),B组中3例再灌注24 h T1WI出现高信号,相应大体标本断面可见出血灶,组织学观察显示B组脑组织损伤较A组严重。C组中8例可见右尾壳核斑片状蓝染区,而D组12例右尾壳核及额顶叶皮质区均见蓝染,测量两组右侧大脑半球伊文氏蓝含量与对侧相比均有显著性差异(P<0.05),两组之间右侧大脑半球伊文氏蓝含量相比有显著性差异(P<0.01),C组中再灌注2 h与再灌注24 h伊文氏蓝含量相比较有显著性差异(P<0.05),D组中再灌注2 h与再灌注24 h伊文氏蓝含量无差异(P>0.05)。结论 缺血再灌注时血脑屏障的损伤随着缺血时间的延长而加重,MRI增强扫描作为一个无创性、可重复性检查方法,有助于评价急性脑缺血再灌注后血脑屏障的状况。

Objective To study the changes of blood-brain barrier (BBB) and its MRI manifestations in the occlusion and reperfusion of the right middle cerebral artery of rats. Methods Forty-four Sprague-Dawley rats were divided into 4 groups. All rats experienced the occlusion and reperfusion of the right middle cerebral artery with thread. Group A and group C were occluded for 2 hours; Group B and group D were occluded for 6 hours. T1WI, T2WI and postcontrast T1WI were performed before reperfusion and 2, 24 hours after reperfusion in group A, group B ( n =10 for each). The outcome of serial MRI was compared with histological studies using light and electron microscopy in 4 animals of group A and group B. In Group C, D ( n =12 for each), the integrity of BBB was investigated using Evans blue (EB) staining brain and the content of EB in the brain tissue was measured by spectrophotometry. Results Postcontrast T1WI showed no enhancement in both group A and B during occlusion. Two hours after reperfusion, patch of enhancement appeared in 4 rats of group A, but all 10 rats in group B showed large piece of obvious enhancement, and 3 rats showed hyper-intensity in T1WI 24 hours after reperfusion. The tissue injury was seen more severe on histological examination in group B compared with group A. In group C, patch blue staining brain was seen in the caudoputamen of 8 animals, while was grossly visible in cortex and caudoputamen of all 12 rats of group D. The content of EB in the right hemisphere was different between group C and D ( P <0.01). The content in the right hemisphere was significantly higher than in the left ( P <0.05). Conclusion With prolonging of the ischemia duration, disruption of the BBB after reperfusion is more severe. The application of MRI is useful to non-invasively and repeatably evaluate the condition of BBB following acute cerebral ischemia.