RESUMO
Mitochondrial dysfunction contributes to brain injury following global cerebral ischemia after cardiac arrest. Carbon monoxide treatment has shown potent cytoprotective effects in ischemia/reperfusion injury. This study aimed to investigate the effects of carbon monoxide-releasing molecules on brain mitochondrial dysfunction and brain injury following resuscitation after cardiac arrest in rats. A rat model of cardiac arrest was established by asphyxia. The animals were randomly divided into the following 3 groups: cardiac arrest and resuscitation group, cardiac arrest and resuscitation plus carbon monoxide intervention group, and sham control group (no cardiac arrest). After the return of spontaneous circulation, neurologic deficit scores (NDS) and S-100B levels were significantly decreased at 24, 48, and 72 h, but carbon monoxide treatment improved the NDS and S-100B levels at 24 h and the 3-day survival rates of the rats. This treatment also decreased the number of damaged neurons in the hippocampus CA1 area and increased the brain mitochondrial activity. In addition, it increased mitochondrial biogenesis by increasing the expression of biogenesis factors including peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, nuclear respiratory factor-2 and mitochondrial transcription factor A. Thus, this study showed that carbon monoxide treatment alleviated brain injury after cardiac arrest in rats by increased brain mitochondrial biogenesis.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Monóxido de Carbono/uso terapêutico , Parada Cardíaca/tratamento farmacológico , Parada Cardíaca/metabolismo , Mitocôndrias/metabolismo , Biogênese de Organelas , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Isquemia Encefálica/etiologia , Proteínas de Ligação a DNA/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Parada Cardíaca/complicações , Masculino , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Fator 1 Nuclear Respiratório/metabolismo , PPAR alfa/metabolismo , Ratos , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: The available evidence suggests that simvastatin plays a beneficial role in lung injury. In addition, statins have been shown to inhibit the activity of inducible nitric oxide synthase (iNOS). The aim of the present study was to investigate the effects of simvastatin on iNOS expression based on a lipopolysaccharide (LPS)-induced septic rat model. METHODS: Thirty-six rats were randomly divided into 3 groups (control group, sepsis group and simvastatin group). A rat model of sepsis was established with LPS. The simvastatin group was pre-treated with simvastatin, whereas the control and sepsis groups were treated with saline before LPS treatment. LPS was injected into the rats in the simvastatin and sepsis groups, while as a negative control, the control group received saline alone. The oxygenation index, expression levels of iNOS and IL-6, and pathological integral of lung injury were analyzed to evaluate the effect of simvastatin on septic rats. RESULTS: Compared with the septic group, significant decreases in the oxygenation index and expression level of iNOS were observed in the simvastatin group. Furthermore, simvastatin treatment resulted in a significant decrease in iNOS levels and the pathological integral of lung injury score in septic rats. CONCLUSION: Simvastatin can relieve acute lung injury induced by sepsis in rats. Decreasing iNOS levels may contribute to the protective role of simvastatin in lung injury.
