Protective effects of P2X7 receptor inhibition in cerebral ischemia/reperfusion injury in rats / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences)
; (12): 1169-1176, 2018.
Article
em Zh
| WPRIM
| ID: wpr-813120
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WPRO
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.
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Índice:
WPRIM
Assunto principal:
Farmacologia
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Fosforilação
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Traumatismo por Reperfusão
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Isquemia Encefálica
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Regulação da Expressão Gênica
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Usos Terapêuticos
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Tratamento Farmacológico
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Receptores Purinérgicos P2X7
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Antagonistas do Receptor Purinérgico P2X
Limite:
Animals
Idioma:
Zh
Revista:
Journal of Central South University(Medical Sciences)
Ano de publicação:
2018
Tipo de documento:
Article