周细胞在慢性脑血流低灌注血-脑脊液屏障损伤中的作用  

Role of pericytes in blood-brain barrier injury under chronic cerebral hypoperfusion

作　　者：曹丹丹[1] 孙静[1] 白云飞[1] 王苗[1] 郭晨佳 崔静[1] 李良[1] Cao DANDan;Sun Jing;Bai Yunfei;Wang Miao;Guo Chenjia;Cui Jing;Li Liang(Department of Pathology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院病理系,北京100069

出　　处：《首都医科大学学报》2018年第4期541-545,共5页Journal of Capital Medical University

基　　金：国家自然科学基金(81571281)~~

摘　　要：目的探讨慢性脑血流低灌注损伤对大脑皮质血-脑脊液屏障及周细胞的影响及可能机制。方法采用大鼠双侧颈总动脉结扎(two-vessel occlusion,2-VO)模型,手术后3、14和30 d检测脑血流量变化。采用荧光免疫组织化学法染色检测周细胞以及纤维蛋白原表达,原代培养周细胞进行细胞增生实验,透射电镜观察血-脑脊液屏障超微结构。结果各模型组均出现脑血流下降,30 d时脑血流仍显著低于对照组。各模型组均有不同程度的纤维蛋白原的血管外渗漏;电镜结果可见基底膜增厚、血管外周围间隙致密物质沉积、星形胶质细胞突起水肿和红细胞血管外渗漏。周细胞数量在术后3、14和30 d均增多;体外实验低浓度纤维蛋白原可促进周细胞增生,而高浓度(20 g/L)纤维蛋白原对周细胞有毒性作用。结论慢性脑血流低灌注破坏大脑皮质血-脑脊液屏障,刺激周细胞增生,纤维蛋白原的渗出可能是引起周细胞增生的主要原因。Objective To investigate the effect of chronic cerebral hypoperfusion（CCH） on the blood-brain barrier（BBB） and pericytes. Methods Bilateral common carotid artery ligation（2-VO） rat model was used. Cerebral blood flow（CBF） was measured at the 3 rd,14 th and 30 th day after 2-VO surgery. Pericyte and fibrinogen expression were detected by fluorescence immunohistochemistry.Primary cultured pericytes were subjected to cell proliferation experiments. Transmission electron microscopy was used to observe the ultrastructure of blood-brain barrier. Results CBF was decreased in each model group,and kept lower at 30 th day after 2-VO. BBB was damaged with fibrin（ogen） extravascular leakage,thickening of the basement membrane,dense deposit in the extravascular space,astrocyte edema,and red blood cell extravascular leakage. The number of pericytes was increased on the 3 rd,14 th,and 30 th day after surgery. In vitro,low concentration of fibrinogen could promote the proliferation of pericytes,while high concentration（20 mg/m L） of fibrinogen had toxic effects on the pericytes. Conclusion CCH disrupts the BBB accompanying with pericytes proliferation,and fibrinogen exudation may be the main cause of pericyte hyperplasia.

关 键 词：慢性脑血流低灌注 血-脑脊液屏障 周细胞 纤维蛋白原 

分 类 号：R743.31[医药卫生—神经病学与精神病学]