首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (4): 541-545.doi: 10.3969/j.issn.1006-7795.2018.04.012

• 缺血性脑损伤的基础与临床研究 • 上一篇    下一篇

周细胞在慢性脑血流低灌注血-脑脊液屏障损伤中的作用

曹丹丹, 孙静, 白云飞, 王苗, 郭晨佳, 崔静, 李良   

  1. 首都医科大学基础医学院病理系, 北京 100069
  • 收稿日期:2018-05-31 出版日期:2018-07-21 发布日期:2018-07-21
  • 通讯作者: 李良 E-mail:liliang@ccmu.edu.cn
  • 基金资助:
    国家自然科学基金(81571281)。

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

Cao Dandan, Sun Jing, Bai Yunfei, Wang Miao, Guo Chenjia, Cui Jing, Li Liang   

  1. Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
  • Received:2018-05-31 Online:2018-07-21 Published:2018-07-21
  • Supported by:
    This study was supported by National Natural Science Foundation of China (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。

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

Abstract: 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 3rd, 14th and 30th 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 30th 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 3rd, 14th, and 30th day after surgery. In vitro, low concentration of fibrinogen could promote the proliferation of pericytes, while high concentration (20mg/mL) 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.

Key words: chronic cerebral hypoperfusion, blood-brain barrier, pericyte, fibrinogen

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