摘要
目的 通过建立一种新的慢性脑低灌注动物模型 ,探讨慢性脑低灌注对血脑屏障的影响以及正常灌注压突破 (NPPB)发生的组织学基础。方法 2 1只 SD大鼠随机分组 :假手术组、模型组动物按动静脉分流术后不同时间点 (12 h、2 4 h、72 h、1w、3w、3m )分组。采用免疫组化方法 ,研究慢性脑低灌注状态下 VEGF蛋白表达的时程变化、血管生成和星形胶质细胞反应。结果 VEGF蛋白表达主要位于血管内皮细胞胞浆 ,在假手术组动物脑组织中呈低水平表达 ,模型组动物脑组织中 VEGF蛋白表达于术后 2 4 h开始升高 ,1w达高峰 ,持续表达到术后 3w ,3m恢复到基础水平。模型组动物脑组织中微血管数量于术后 1w开始明显增加 ,一直维持到术后 3m ,而星形胶质细胞未见明显的增生反应。结论 慢性脑低灌注可持续性诱导 VEGF蛋白表达 ,并与血管生成有一定关系 ;血管生成与星形胶质细胞反应不协调影响了血脑屏障的结构完整性 ,可能是导致 NPPB的一个重要因素。
Objective A new animal model was developed to investigate the effect of chronic cerebral hypoperfusion on blood-brain barrier(BBB) and the histological basis of normal prefusion pressure breakthrough(NPPB). Methods Twenty-one SD rats were randomly divided into groups as follows:sham-operation group,the animals in the model group were assigned on the basis of various time points(12h,24h,72h,1w,3w,3m) after arteriovenous shunting. Immunohistochemical techniques were used to evaluate the time course of expression of VEGF protein,angiogenesis and astrocytic reactivity during chronic cerebral hypoperfusion. Results VEGF protein expression mainly localized to vascular endothelial cells by immunohistochemistry. There were low VEGF protein levels in rat brains of the sham-operation group. However,VEGF protein levels began to increase in rat brains of the model groups at 24h postoperatively,peaked at 1w,sustained until 3w,and returned to basal expression at 3m. Microvascular density in rat brains increased significantly at 1w postoperatively in the model groups by immunohistochemical means,and remained elevated through 3m postoperatively,whereas no prominent astrocytic reactivity was found in rat brains of all groups. Conclusion This results demonstrates that chronic cerebral hypoperfusion can induce sustained upregulation of VEGF protein expression which may be related to angiogenesis. No corresponding astrocytic reactivity during angiogenesis may be an important factor for the BBB integrity and the occurrence of NPPB.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2003年第5期406-408,共3页
Journal of Apoplexy and Nervous Diseases
