Desferroxamine preconditioning protects against hypoxia in neurons
10.3760/cma.j.issn.1006-7876.2009.02.016
- VernacularTitle:去铁敏预处理对神经元缺氧性损伤的保护作用
- Author:
Yunxia LI
;
Suju DING
;
Qing ZHAN
;
Lin XIAO
;
Wei GUO
- Publication Type:Journal Article
- Keywords:
Desferoxamine;
Ischemic preconditioning;
Infarction middle cerebral artery;
Hypexia-inducible factor 1,αlpha subunit;
Erythropoietin
- From:
Chinese Journal of Neurology
2009;42(2):119-124
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the possible effects and underlying mechanisms of desferroxamine (DFO) preconditioning against hypoxia in neurons. Methods Cortical neurons were cultured in DFO under ischemia condition of oxygen-glucose deprivation (OGD). Cell viability was determined by cell counting kit-8 (CCK-8) method; apoptotic cell ratio was examined with Hoechst 33342 staining; the morphological change was observed. Middle cerebral artery was occluded with or without DFO administration to establish the cerebral ischemia rat model. Infarct sizes were examined by TIC staining, and the neurological severity score was evaluated. Meanwhile immunofluorescent staining was employed to detect the protein synthesis of hypoxia inducible factor-1 (HIF-1) and erythropoietin (EPO), RT-PCR was performed to detect the mRNA expression of HIF-1 and EPO as well Results Neuronal viability kept in 49% (OGD group was 25%, t =8. 544, P<0. 05), the rate of apoptosis was 38% (OGD group was 30%, t = 4. 409, P <0.05 ) after administration of DFO (post-DFO) , the morphology of neurons improved. In the model of focal cerebral ischenfia of 30 mg/kg group, neurological severity score was reduced, the percentage of brain infarct decreased 8.5% (t=4.649, P<0.05) 3 days post-DFO(vs control). In the 100 mg/kg group, neurological severity score was 7.44 ±0.39 (t=2.903, P<0.05 ) ,5.60±0.47 (t=10.143, P < 0.01 ) ,6.97 ±0.73 (t=3.142, P<0.05 ), the percentage of brain infarct decreased 12. 0% (t=5.056, P<0.05), 32.3% (t =10.993, P<0.01), 10.6% (t =4.385, P<0.05)2,3 and7 days post-DFO(vs control), respectively. Immunofluorescent staining found synthesis of HIF-1α and EPO in cultured cortex neurons after DFO pretreated; HIF-1α and EPO were upregulated in the neurons of rat brain after DFO pretreated. The mRNA of HIF-1α and EPO upregulated in vivo and in vitro. Conclusion DFO preconditioning can protect the brain against ischemic damage, which is related to the protective effect on neurons. The mechanism of DFO preconditioning may be involved in the expression of HIF-1α and EPO in vivo and in vitro.
