Page 25 - 2021年15期

原儿茶醛对大鼠脑缺血再灌注损伤后神经血管单元稳态破坏的

保护作用 Δ

＊
冯 晋 ，徐娅玲，孟庆婷，颜汉文，何芳雁（云南中医药大学中药学院，昆明 650000）
#
中图分类号 R285.5 文献标志码 A 文章编号 1001-0408（2021）15-1811-07
DOI 10.6039/j.issn.1001-0408.2021.15.04

摘 要 目的：研究原儿茶醛对大鼠脑缺血再灌注损伤（CIRI）后神经血管单元（NVU）稳态破坏的保护作用。方法：将SD大鼠随
机分为假手术组、模型组和原儿茶醛高、低剂量组（10、20 mg/kg），每组11只。给药组大鼠灌胃相应药物，假手术组和模型组大鼠
灌胃等体积水，灌胃体积均为10 mL/kg，每日1次，连续5 d。末次给药后，采用线栓法复制大鼠CIRI模型，采用透射电镜观察大
鼠脑组织中NVU超微结构的变化；采用Western blot法检测大鼠脑组织中NVU相关蛋白[神经元标志蛋白（MAP-2）、胶质纤维酸
性蛋白（GFAP）、水通道蛋白（AQP-4）]的表达水平；采用免疫荧光染色法检测大鼠大脑皮层中上述蛋白的阳性表达水平。结果：
与假手术组比较，模型组大鼠血脑屏障（BBB）结构被严重破坏，血管腔变窄，内皮细胞外侧严重水肿，基底膜厚薄不一；神经元核
固缩，周围组织存在大面积水肿；胶质细胞结构严重破坏，胞体皱缩、细胞器损失；脑组织（或大脑皮层）中 MAP-2 蛋白表达水平
（或阳性表达水平）均显著降低（P＜0.05或P＜0.01），GFAP、AQP-4蛋白表达水平（或阳性表达水平）均显著升高（P＜0.01）。经原
儿茶醛干预后，大鼠BBB损伤减轻，血管腔和基底膜形态未完全被破坏；神经元损伤减轻，神经元核固缩减少，染色质均匀、异染
色质减少；胶质细胞结构破坏减轻，脑组织中GFAP、AQP-4（低剂量组除外）蛋白表达水平以及大脑皮层中MAP-2、GFAP蛋白阳
性表达水平均显著逆转（P＜0.05或P＜0.01）。结论：原儿茶醛可保护CIRI模型大鼠的NVU稳态免受破坏；其作用机制可能与上
调大鼠大脑皮层中MAP-2蛋白表达，下调脑组织中GFAP、AQP-4蛋白表达有关。
关键词 原儿茶醛；脑缺血再灌注损伤；神经血管单元；大脑皮层；大鼠

Protective Effect of Protocatechuic Aldehyde on Neurovascular Unit Homeostasis Damage in Rats after
Cerebral Ischemia-reperfusion Injury
FENG Jin，XU Yaling，MENG Qingting，YAN Hanwen，HE Fangyan（School of TCM，Yunnan University of
TCM，Kunming 650000，China）

ABSTRACT OBJECTIVE：To observe the protective effect of protocatechuic aldehyde （PAL） on neurovascular unit （NVU）
homeostasis damage in rats after cerebral ischemia-reperfusion injury（CIRI）. METHODS：SD rats were randomly divided into
sham operation group，model group，PAL high-dose and low-dose groups （10，20 mg/kg），with 11 rats in each group.
Administration groups were given relevant medicine intragastrically. Sham operation group and model group were given the same
volume of normal saline intragastrically，10 mL/kg once a day，for 5 days. After last administration，CIRI model was induced by
suture method；the ultrastructural changes of NVU were observed by transmission electron microscope. Western blot assay was used
to detect the expression of NUV related proteins（MAP-2，GFAP，AQP-4）in cerebral tissue. Immunofluorescence staining was
used to observe the positive expression of above proteins in cerebral cortex. RESULTS：Compared with sham operation group，
blood-brain barrier（BBB）structure of model group was destroyed severely，the vascular lumen became narrower，lateral edema of
endothelial cells was severe，and the thickness of basement membrane varied；the nuclei of neurons were pyknosis and there was a
large area of edema in the surrounding tissues；the structure of glial cells was seriously damaged，the cell body was shrunk and
organelles were lost；protein expression（or positive expression）of MAP-2 in brain tissue（or cerebral cortex）were significantly
decreased （P＜0.05 or P＜0.01）， while protein expression （or positive expression） of GFAP and AQP-4 were increased
significantly （P＜0.01）. After PAL intervention，the rats had less BBB damage，and the morphology of vascular lumen and
basement membrane were not completely destroyed；the damage of neurons was alleviated，the pyknosis of neurons was decreased，
the chromatin was homogeneous and the heterochromatin was
Δ 基金项目：国家自然科学基金资助项目（No.81660677）；云南省
decreased；the damage of glial cell structure was alleviated；
科技计划项目基础研究专项（No. 202001AT070138）；云南科技计划项
protein expression of GFAP and AQP-4（except for low-dose
目中医联合重点项目[No.2017FF117（-004），No.2018FF001（-007）]；云
group） in cerebral tissue and positive expression of MAP-2
南省教育厅科学研究基金项目（No.2020Y0208，No.2020Y0212）
and GFAP protein in cerebral cortex were reversed
＊硕士研究生。研究方向：中药药理学。E-mail：1285187026
@qq.com significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： PAL
# 通信作者：实验师，硕士。研究方向：中药药理学。E-mail： can protect the stability of NVU from damage in CIRI model
735137511@qq.com rats； the mechanism may be related to up-regulating the

中国药房 2021年第32卷第15期 China Pharmacy 2021 Vol. 32 No. 15 ·1811 ·