Correlation between Nurr1 expression and drug resistance in the brain of rats with epilepsy
OBJECTIVE: To investigate the correlation between nuclear receptor related 1 (Nurr1) expression and drug resistance in the brain of rats with epilepsy. MATERIALS AND METHODS: A total of 60 adult male Sprague-Dawley rats were selected, and the animal model of epilepsy was established by electrical stimulation. These rats were randomly divided into the control group and the drug-resistant group. The model of drug-resistant epilepsy was screened with phenytoin (PHT) and phenobarbital (PB); the
... bital (PB); the hippocampus and temporal lobe cortex tissues were isolated from rats; the messenger ribonucleic acid (mRNA) and protein levels of Nurr1 in the hippocampus and cortex tissues of the two groups of rats were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immuno-histochemistry, respectively. The budding tissue marker growth-associated protein-43 (GAP43) in hippocampus tissues were labeled by immuno-fluorescence staining; the mRNA and protein levels of indicators related to drug-resistant epilepsy , including leukemia-associated phenotype (LAP), multi-drug resistance protein (MRP), P-glycoprotein (P-gp) and monocyte chemoat-tractant protein-1 (MCP-1), were further detected. Pearson correlation analysis was used to analyze the correlations of the protein level of Nurr1 with drug-resistant indicators. RESULTS: The mRNA and protein levels of Nurr1 in hippocampus tissues of the drug-resistant group were significantly increased compared with those of the control group (p < 0.05). In temporal lobe cortex tissues, there was no significant difference in the mRNA level of Nurr1 between the control group and the drug-resistant group (p > 0.05). The immunohistochem-istry results showed that the fluorescence intensity of GAP3 in hippocampus tissues of the drug-resistant group was significantly higher than that of the control group. The mRNA and protein levels of epilepsy-related indicators, LAP, MRP, P-gp and MCP-1 in hippocampus tissues of drug-resistant group were significantly up-regulated compared with those of the control group (p < 0.05). Pearson correlation analysis indicated that the protein level of Nurr1 in hippo-campus tissues was positively correlated with those of LAP, MRP, P-gp and MCP-1 in the corresponding regions (p < 0.05). CONCLUSIONS: Nurr1 enhances the drug resistance of epilepsy in rats by up-regulating the expression of proteins related to drug resistance.