Effect of β-sodium aescinate on hypoxia-inducible factor-1α expression in rat brain cortex after cardiopulmonary resuscitation

BACKGROUND: This study was undertaken to investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in rat cerebral cortex and the effects of beta-sodium aescinate (SA) administration after return of spontaneous circulation (ROSC). METHODS: Sixty rats were divided into three groups: SA group, injected intraperitoneally with SA instantly after ROSC; control group, injected intraperitoneally with normal saline; and shamoperated group, without cardiac arrest or SA. The cardiac arrest model was established using asphyxiation and intravenous potassium chloride. Blood was sampled 1, 6, 12, and 24 hours after ROSC. Protein and mRNA levels of HIF-1 alpha, VEGF and EPO were detected in the cerebral cortex by immunohistochemistry and real-time RT-PCR; serum levels of NSE and S100 beta were determined by enzyme-linked immunosorbent assays. RESULTS: Serum S100 beta and NSE were significantly increased in the control group versus the sham-operated group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1 alpha, VEGF and EPO were significantly increased in the control rats (P<0.05). Serum NSE and S100 beta were significantly decreased in the SA group versus the control group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1 alpha, VEGF and EPO were significantly increased in the SA group (P<0.05). CONCLUSIONS: The expression of HIF-1 alpha is increased in rat cerebral cortex after ROSC, and SA up-regulates the expression of HIF-1 alpha. The up-regulation of HIF-1 alpha improves the resistance of the cortex to ischemia and hypoxia and contributes to neuroprotection, possibly because of up-regulation of EPO and VEGF expression.