Astragalus polysaccharide protects against blood-brain barrier damage in MCAO rats by inhibiting P2X7R channel.
10.12122/j.issn.1673-4254.2022.11.15
- Author:
Qiao YUAN
1
;
Li Ying XIE
2
;
Chao Jun CHEN
2
Author Information
1. Guangzhou University of Chinese Medicine, Guangzhou 510800, China.
2. Department of Encephalopathy, Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou 510800, China.
- Publication Type:Journal Article
- Keywords:
P2X7R channel;
astragalus polysaccharides;
blood-brain barrier;
matrix metalloproteinase-9
- MeSH:
Animals;
Rats;
Rats, Sprague-Dawley;
Blood-Brain Barrier;
Infarction, Middle Cerebral Artery;
Matrix Metalloproteinase 9;
Polysaccharides/pharmacology*;
Evans Blue;
Oxygen;
Glucose;
Adenosine Triphosphate
- From:
Journal of Southern Medical University
2022;42(11):1705-1711
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the protective effect of astragalus polysaccharide (APS) against blood-brain barrier in a rat model of middle cerebral artery occlusion (MCAO) and the role of P2X7R channel in the protective mechanism.
METHODS:In rat microglial cell models of oxygen and glucose deprivation (OGD) or ATP treatment, the formation of blood-brain barrier in vitro was assessed using the leak test, and the effect of APS on the permeability of the blood-brain barrier was determined using LC-MS. In 12 SD rats, MCAO model was established followed by treatment with intraperitoneal injection of normal saline (n= 6) or APS (45 mg/kg, n=6) for 3 consecutive days, with another 6 rats without MCAO receiving saline injections as the control group. The permeability of the blood-brain barrier of the rats was evaluated by determining Evans blue (EB) extravasation, and ATP content in the brain tissue was detected using ELISA; the expression levels of matrix metalloproteinase-9 (MMP-9) and P2X7R in the brain tissue were detected with Western blot.
RESULTS:In the in vitro cell model of OGD or ATP treatment, APS treatment obviously promoted the repair of blood-brain barrier integrity. In the rat models, the EB content in the brain tissue and the blood-brain barrier permeability increased significantly in MCAO+saline group and MCAO+APS group as compared with those in the control group (P < 0.01). Compared with saline treatment, APS treatment significantly decreased EB content in the brain tissue and improved the blood-brain barrier permeability in the MCAO rats (P < 0.05). MCAO caused a significant reduction of ATP content and obviously increased the expression levels of MMP-9 and P2X7R in the brain tissue of the rats (P < 0.01), and these changes were significantly alleviated after APS treatment (P < 0.01 or 0.05).
CONCLUSION:APS can protect the brain tissue of MCAO rats by stabilizing the internal environment, down-regulating the expression of MMP-9 and improving the permeability of blood-brain barrier under cerebral ischemia and hypoxia, and its mechanism may involve the inhibition of P2X7R channel.
