Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

Acta Cir Bras. 2018 Feb;33(2):117-124. doi: 10.1590/s0102-865020180020000003.

Abstract

Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI).

Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis.

Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C.

Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins
  • Brain Ischemia / metabolism*
  • Brain Ischemia / prevention & control
  • Cardiotonic Agents / pharmacology*
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mitochondrial Proteins / metabolism*
  • Neuroprotective Agents / pharmacology
  • Phosphocreatine / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / prevention & control
  • X-Linked Inhibitor of Apoptosis Protein / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Cardiotonic Agents
  • DIABLO protein, human
  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • Neuroprotective Agents
  • X-Linked Inhibitor of Apoptosis Protein
  • Phosphocreatine
  • Caspase 3