Hypoxia-inducible factor-1(HIF-1) is a key factor in hypoxic response of cells.It plays an important role in embryonic development,cerebral infarction,cerebral hemorrhage,hypoxic-ischemic encephalopathy,neurodegenerative diseases,cancers and other physiological or pathological processes.Studies have confirmed that in developing rats,the expression of HIF-1 α mRNA and HIF-1α in hippocampus after status epilepsy enhanced obviously,and it is related to proliferation of neural stem cells.Although some experiments have explored the relationship between certain signaling pathways and HIF-1 α,no experiments come to the signal-regulation in the expression of HIF-1α after epilepsy.

Objective To investigate the correlation between hypoxia-inducible factor-1α (HIF-1α) expression and activation of phosphatidyl inositol 3-kinase and serine/threonine kinase signal pathway in the hippocampus of developing rats after status epilepticus (SE).Methods Fifty-four SD rats aged 21 days were randomly divided into control group (n=24),SE group (n=24),wortmannin treatment group (n=6); SE rat models of the SE group were induced by intraperitoneal injection of 1％ 1,5-Pentamethylenetetrazole (PTZ); rats of the control group received injection of normal saline (NS); for wortmannin treatmnet group,the rats received intraperitoneal injection ofwortmannin 30 minutes before the inducement; the brain tissues were harvested from the rats at 1,4,8 and 24 h after the inducement,but only at 4 h in the wortmannin treatment group.The HIF-1α and Akt positive cells were detected with irnmunohistochemistry method.HIF-1α,Akt and p-Akt protein expressions were measured by Western blotting.Results In SE group,the HIF-1α expression began to occur at 1 h,significantly increased at 4 h after inducement,reached the peak level at 8 h,and began to decrease at 24 h; Akt protein positive cells showed no significant difference between each two time points; the p-Akt protein was significantly increased at 1 h,reached the peak level at 4 h and began to decrease at 8 h.However,the expression levels of HIF-1α and p-Akt protein in the control group were extremely low at each time point.So,the HIF-1α expression level in the SE vehicle group was significantly higher than that in the control group (P＜0.05); the p-Akt protein expression in SE group at 1,4 and 8 h was significantly higher than that in the control group (P＜0.05).The changes of Akt protein in the SE group were not time-dependent,and no significant difference was evident when it was compared with that of the control group (P＞0.05).Using wortmannin,the PI3K/Akt specific inhibitor,HIF-lα protein expression was significantly decreased when it was compared with the SE vehicle group (P＜0.05).Conclusion After status epilepticus in the developing rats,the PI3K/Akt signaling pathway is activated and the pathway involves in regulating the HIF-1α expression.