INS患者GR、NF-kB和AP-1水平与糖皮质激素治疗的关系

Purpose To invesigate the effect of glucocortioid on the nuclear protein level of glucocorticoid receptor (GR), activator protein-1 (AP-1) and nuclear factor-kappa B(NF-kB), and the relationship between this effect and the glucocorticoid sensitivity in idiopathic nephrotic syndrome (INS). Methods Einghteen patients with INS, 10 were glucocorticoid sensitive (GCS) group and 8 were in glucocorticoid resistant (GCR) group, followed up for 24 weeks. The subunits of GR, AP-1 and NF-kB in INS were detected by super-shift assay. The nuclear protein level of components of activated GR, AP-1 and NF-kB was detected by Western Blotting assay. Results The nuclear protein level of GR-a obviously increased after a week of therapy with methyl-prdnisolone and there was no difference between two groups. Super-shift assay indicated that the antibodies to p65 and p50 produced a retardation of the NF-kB/DNA band in PBMC of INS patients, and there was obvious difference of p65 between glucocorticoid sensitive (GCS) and glucocorticoid resis-tant (GCR) group. AP-1 was composed of c Jun and c-Fos in PBMC of INS patients. The protein level of nuclear c-Fos was persistently higher in GCR than in GCS before and during the GC treatment. Conclusions The nuclear protein level of p65 and c-Fos may play an important role in the pathogenesis of steroid resistance.