Protective effects of P2X7 receptor inhibition in cerebral ischemia/reperfusion injury in rats.
10.11817/j.issn.1672-7347.2018.11.001
- Author:
Yinling CHEN
1
;
Yuanyuan TANG
1
;
Xuhui TONG
1
;
Jianfeng WU
1
;
Yan LI
2
;
Shuying DONG
1
Author Information
1. Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu Anhui 233030, China.
2. Department of Pathophysiology, School of Basic Medicine, Bengbu Medical College, Bengbu Anhui 233030, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Brain Ischemia;
drug therapy;
prevention & control;
Gene Expression Regulation;
drug effects;
Phosphorylation;
drug effects;
Purinergic P2X Receptor Antagonists;
pharmacology;
therapeutic use;
Rats;
Receptors, Purinergic P2X7;
Reperfusion Injury;
drug therapy;
prevention & control
- From:
Journal of Central South University(Medical Sciences)
2018;43(11):1169-1176
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the protective effects of P2X7 receptor (P2X7R) inhibitor against cerebral ischemia/reperfusion (I/R) injury in rats and the possible mechanisms.
Methods: The neurological deficit of rats was evaluated by Longa score. The infarct volume was examined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression levels of extracellular signal-regulated kinase (ERK), phosphorylation extracellular signal-regulated kinas p-ERK), connexin 43 (Cx43), Bax, Bcl-2 and cleaved caspase-3 were detected by Western blot.
Results: Compared with sham group, the neurobehavioral score (P<0.05) and cerebral infarct volume (P<0.01) of rats in I/R group was increased. Compared with I/R group, brilliant blue G (BBG, the antagonist of P2X7R) or PD98059 (the inhibitor of EKR kinase) could reduce the neurobehavioral score (P<0.01) and cerebral infarct volume significantly (P<0.05). The neurobehavioral score and cerebral infarct volume was further decreased (P<0.05) when rats were treated with both BBG and PD98059. Compared with I/R group, the expression levels of p-ERK, Cx43, cleaved caspase-3 and the ratio of Bax/Bcl-2 were decreased by BBG or PD98059 pretreatment, and the protective effects were further enhanced when rats were treated with both BBG and PD98059 (P<0.05).
Conclusion: Inhibition of P2X7R reduces the cerebral I/R injury of rats. ERK inhibition is probably involved in the protective effects of P2X7R inhibitor against cerebral I/R injury, which may be related to the reduction of Cx43 and cleaved caspase-3, and the ratio of Bax/Bcl-2.
