Construction of 3D blood-brain barrier organoid oxygen-glucose deprivation model and exploration of the protective effect of Guanxinning injection
10.16438/j.0513-4870.2021-1871
- VernacularTitle:3D血脑屏障类器官氧糖剥夺模型的构建及冠心宁注射液的保护作用探究
- Author:
Hong-ying DU
1
;
Zhi-feng XUE
1
;
Zhong-ting XIA
2
;
Shuang HE
1
;
Jian YANG
1
;
Yan ZHU
1
Author Information
1. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Chinese Medicine New Drug Research and Development Center, Tianjin International Biomedical Research Institute, Tianjin 300457, China
2. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Increasepharm (Tianjin) Institute Co., Ltd., Tianjin 300385, China
- Publication Type:Research Article
- Keywords:
blood-brain barrier;
organoid;
oxygen-glucose deprivation/reoxygenation;
ischemic stroke;
Guanxinning injection
- From:
Acta Pharmaceutica Sinica
2022;57(10):3086-3094
- CountryChina
- Language:Chinese
-
Abstract:
The blood-brain barrier (BBB) plays an important role in maintaining the homeostasis of the central nervous system. BBB is disrupted in many neurological disorders such as ischemic stroke and Alzheimer's disease. Traditional Chinese medicine has great potential to prevent ischemic stroke, but the lack of clinically relevant models has been a challenge. We adapted a BBB organoid model formed by human brain microvascular endothelial cells (HBMEC), human astrocytes (HA), and human brain vascular pericytes (HBVP), and established conditions for oxygen-glucose deprivation/reoxygenation (OGD/R) on the cell vitality, barrier permeability, as well as BBB signature marker expression. The protective effect of Guanxinning injection (GXNI) on OGD/R-induced BBB dysfunction was then investigated in the organoid model. The results showed that OGD/R decreased BBB organoid cell viability, increased permeability (leakage), decreased the level of tight junction proteins zonula occludens-1 (ZO-1), claudin-5, occludin and P-glycoprotein (P-gp). GXNI significantly prevented OGD/R-induced BBB disruption such as the decreased cell viability and increased permeability. This study provides a new human cell-derived 3D ischemic brain disease model for central nervous system-targeted drug research and development and demonstrates that a Chinese injection medicine GXNI effectively protects BBB dysfunction in vitro.
