Protective effect of histone acetylation against cortical injury in neonatal rats / 中国当代儿科杂志
Chinese Journal of Contemporary Pediatrics
; (12): 81-87, 2017.
Article
em Zh
| WPRIM
| ID: wpr-351396
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effect of histone acetylation against hypoxic-ischemic cortical injury in neonatal rats.</p><p><b>METHODS</b>A total of 90 neonatal rats aged 3 days were divided into three groups: sham-operation, cortical injury model, and sodium butyrate (a histone deacetylase inhibitor) treatment. The rats in the model and the sodium butyrate treatment groups were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg), and then right common carotid artery ligation was performed 2 hours later and the rats were put in a hypoxic chamber (oxygen concentration 6.5%) for 90 minutes. The rats in the sham-operation group were intraperitoneally injected with normal saline and the right common carotid artery was only separated and exposed without ligation or hypoxic treatment. The rats in the sodium butyrate treatment group were intraperitoneally injected with sodium butyrate (300 mg/kg) immediately after establishment of the cortical injury model once a day for 7 days. Those in the sham-operation and the model groups were injected with the same volume of normal saline. At 7 days after establishment of the model, Western blot was used to measure the protein expression of histone H3 (HH3), acetylated histone H3 (AH3), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (BAX), cleaved caspase-3 (CC3), and brain-derived neurotrophic factor (BDNF). Immunofluorescence assay was used to measure the expression of 5-bromo-2'-deoxyuridine (BrdU) as the cortex cell proliferation index.</p><p><b>RESULTS</b>The sodium butyrate treatment group had a significantly lower HH3/AH3 ratio than the model group (P<0.05), which suggested that the sodium butyrate treatment group had increased acetylation of HH3. Compared with the model group, the sodium butyrate treatment group had a significant increase in Bcl-2/Bax ratio, a significant reduction in CC3 expression, and a significant increase in BDNF expression (P<0.05). The sodium butyrate treatment group had a significant increase in the number of BrdU-positive cells in the cortex compared with the model group (P<0.05), and BrdU was mainly expressed in the neurons.</p><p><b>CONCLUSIONS</b>Increased histone acetylation may protect neonatal rats against cortical injury by reducing apoptosis and promoting regeneration of neurons. The mechanism may be associated with increased expression of BDNF.</p>
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Base de dados:
WPRIM
Assunto principal:
Patologia
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Acetilação
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Histonas
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Córtex Cerebral
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Ratos Sprague-Dawley
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Apoptose
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Fator Neurotrófico Derivado do Encéfalo
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Ácido Butírico
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Usos Terapêuticos
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Animais Recém-Nascidos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
Zh
Revista:
Chinese Journal of Contemporary Pediatrics
Ano de publicação:
2017
Tipo de documento:
Article