[Protective effects of P2X7 receptor inhibition in cerebral ischemia/reperfusion injury in rats].

Abstract

OBJECTIVE:

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.

• Authors: Yinling Chen, Yuanyuan Tang, Xuhui Tong, Jianfeng Wu, Yan Li, Shuying Dong
• Journal: Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences (Zhong Nan Da Xue Xue Bao Yi Xue Ban) Vol. 43 Issue 11 Pg. 1169-1176 (Nov 28 2018) ISSN: 1672-7347 [Print] China
• PMID: 30643059 (Publication Type: Journal Article)

Chemical References

• Purinergic P2X Receptor Antagonists
• Receptors, Purinergic P2X7

Topics

• 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)