correlational study of hypoxia-inducible factor-1 and pharmacoresistance of sprague-dawley rat temporal lobe epilepsy model kindled by coriaria lactone

Abstract

Objective 　To investigate changes in the expression of hypoxia-inducible factor-1 (HIF-1) in different brain regions in a pharmacoresistance model of temporal lobe epilepsy, and explore its relation to the expression of drug resistance gene/protein multidrug-resistance-gene1(MDR1)/P-glycoprotein (Pgp). Methods 　A kindling model of pharmacoresistant temporal lobe epilepsy was developed by injecting Sprague-Dawley (SD) rats with coriaria lactone (CL). Normal SD rats were injected with normal sodium (NS) served as control group. The expressions of HIF-1, MDR1/Pgp in brain tissues were detected by real-time fluorescence-based quantitative polymerase chain reaction (RQ-PCR), immunohistochemistry (IHC), Western blotting, respectively. Results 　IHC showed that the expressions of HIF-1 in neurons and glial cells were higher in the hippocampus and temporal cortex than in other brain regions in kindled rats, and the regional distribution of HIF-1 was similar to that of Pgp. RQ-PCR and Western blotting showed that the expressions of HIF-1 in the hippocampus and temporal cortex were higher in kindled group than in control group (P < 0.05), and the expressions of MDR1/Pgp in gene and protein levels were consistent with the alterations of HIF-1 in both groups. Conclusion 　HIF-1 expressions in hippocampus and temporal cortex in kindled rats are higher than those in control rats, and it corresponds to the regional distribution of Pgp. The correlation of HIF-1 and MDR1/Pgp expressions indicates that HIF-1 may be related to the drug resistance of refractory temporal lobe epilepsy.