RESUMEN
Objective To explore the expressions of hypoxia-inducible factor-1 alpha (HIF- lα)and nestin in the hippocampus of developing rats after pentylenetetrazol (PTZ)-induced starus epilepticus (SE),and the correlation between HIF-1α level and proliferation of neural stem cells (NSCs). Methods A total of 768 SD rats,including rats of postnatal 7 days (P7,n-192),rats of postnatal 14 days (P14,n=192),rats of postnatal 21 days (P21,n=192) and rats of postnatal 28 days (P28,n=192),were equally randomized into vehicle group (n=96) and control group (n-96),respectively; SE rat models of the vehicle group were induced by intraperitoneal injection of 1％ PTZ (80 mg/kg); and rats of the control group were received injection of normal saline (NS); 6 and 12 h,and 1,2,3 and 7 d after the inducement,the mRNA and protein expressions of HIF-1α in the hippocampus of rats in these 8 groups were examined by RT-PCR and immunohistochemistry, respectively. Another 48 21-d- old SD rats were equally randomized into vehicle I group (n=24) and intervention group (n=24); and rats in the intervention group received injection of HIF-lα antisense oligodeoxynucleotides (ASODN) into the right hippocampus and NS into the left hippocampus; 6 h after the injection,these 48 rats were induced into SE models by intraperitoneal injection of 1％ PTZ (80 mg/kg); 2 d after the inducement, the mRNA expression of HIF-1α in the hippocampus was examined by RT-PCR; and 7 and 14 d after theinducement, the protein expressions of HIF-1α and nestin in the hippocampus were examined by immunohistochemistry. Results The mRNA expression of HIF-1 α in the hippocampus of all the rats in the vehicle group after SE increased significantly with similar trend.Six h after SE,the HIF-1α mRNA expression significantly decreased with time prolongation (P＜0.05). Major HIF-1α positive cells were located in different areas at different time after SE. In intervention experiment, the HIF-1α mRNA expression 2 d after SE and the number ofnestin positive cells 7 and 14 d after SE in the vehicle I group and the left hippocampus of intervention group(being intervented with ASODN) obviously decreased as compared with those in the right hippocampus (being intervented with NS,P＜0.05). Conclusion The mRNA and protein expressions of HIF-1α in the hippocampus of developing rats are enhanced after SE with a correlation of age-in-days; correlativity between HIF-1α and proliferation of NSCs might exist after SE.