Effect of activation of nuclear factor-κB/hypoxia-inducible factor-1α pathway on the hippocampal neurodegeneration caused by status epilepticus in rats / 中华神经科杂志

ABSTRACT

Objective To observe the roles of nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1 o (HIF-1 α) in hippocampal neurodegeneration of status epilepticus (SE) rats, and explore whether HIF-1α activation is regulated by NF-κB.Methods A total of 110 male Sprague-Dawley rats were randomly divided into seven groups (1) Control group treated with saline (control, n =15), (2) sham group implanted cannula into lateral ventricle and treated with saline (sham, n =15), (3) SE group treated with pilocarpine (SE, n =20), (4) NF-κB activity inhibitor pyrrolidine dithiocarbamate (PDTC) group treated only with PDTC (PDTC, n =15), (5) SE + PDTC group treated with pilocarpine plus PDTC (SE + PDTC, n =15), (6) SE + HIF-1o siRNA group implanted cannula into lateral ventricle and treated with pilocarpine plus HIF-1 α siRNA (SE + HIF-1α siRNA, n =15), (7) SE + control siRNA group implanted cannula into lateral ventricle and treated pilocarpine plus control siRNA (n =15).SE was induced by injecting lithium chloride and pilocarpine.The seizure of rats was observed.The protein expressions of NF-κB and HIF-1 α in hippocampus of rats were examined by Western blotting.The degenerating neurons in hippocampus were detected by Fluoro-Jade C (FJC) staining.Results Twenty-four hours after termination of SE, the nuclear protein expressions of NF-κB and HIF-1α in hippocampus of rats were increased in SE group (0.57 × 0.06, 0.47 ± 0.07) compared with those in control group (0.23 ± 0.03, 0.20 ± 0.03;P ＜0.05);and compared with SE group PDTC significantly decreased the nuclear protein expressions of NF-κB and HIF-1 α in SE + PDTC group (0.23 ± 0.03, 0.14 ± 0.03;P ＜ 0.05);in SE + PDTC group the numbers of FJC positive cells in CA1 area (28.33 ±5.03) were decreased compared with that in SE group (76.67 ± 13.32);HIF-1 o siRNA injected into lateral ventricle of rats significantly decreased the expression of HIF-1α in hippocampus (0.22 ±0.03) and the number of FJC positive cell in CA1 area (27.34 ±7.02) in SE + HIF-1α siRNA group compared with those in SE group (0.39 ±0.06, 76.67 ± 13.32;P ＜0.05).Conclusions These data suggest that SE can result in activation of NF-κB/HIF-1o pathway in brain.Inhibition of the pathway can attenuate hippocampal neurodegeneration caused by SE, which has the brain protective effect.