目的：探讨戊四氮(PTZ)所致大鼠严重惊厥发作模型中核因子κB(NFκB)活化与神经细胞凋亡的关系。方法：42只大鼠随机分为7组,即对照组、致惊后3h、6h、12h、24h、48h和吡咯啉烷二硫代氨基甲酸盐(PDTC)+PTZ组。免疫组织化学法检测海马CA1区NFκB亚基p65核移位;TUNEL和流式细胞仪检测海马细胞凋亡。结果：流式细胞仪和TUNEL法显示惊厥发作后有细胞凋亡的发生,24h达高峰,与对照组相比分别为(12.54±4.99)%vs(2.24±0.57)%和(61.62±4.99)个/gcsvs(3.35±0.89)个/gcs,P均<0.001;对照组大鼠海马未见p65核移位细胞,而致惊后p65核移位细胞显著上调,24h达高峰(32.30±4.71)个/gcs。PDTC预处理组与致惊24h组相比p65核移位及细胞凋亡明显减少。结论：NFκB活化在严重惊厥发作所致的细胞凋亡发生中发挥重要作用;PDTC可通过抑制NFκB的表达而减少惊厥后的细胞凋亡。

OBJECTIVE: The effects of nuclear factor-kappaB (NF-κB) on neurons in the brain remain controversial. This study examined the relationship between NF-κB activation and neuronal apoptosis in rats with pentylenetetrazol (PTZ)-induced serious seizures. METHODS: Forty-two rats were randomly assigned into a Seizure group, a pyrrolidine dithiocarbamate (PDTC)-pretreatment seizure group and a Normal control group. The model of serious seizures was induced by an intraperitoneal injection of PTZ (60 mg/kg). Rats in the Seizure group were sacrificed 3, 6, 12, 24, and 48 hrs after seizure induction. The PDTC pretreatment group was administered with PDTC (100 mg/kg) 1 hr before PTZ injection, and sacrificed 24 hrs later. The immunohistochemistry method was used to detect the activity of NF-κB protein in the CA1 region of the hippocampus. The in situ dUTP end-labeling (TUNEL) technique and flow cytometry (FCM) were used to measure the neuronal apoptosis in the hippocampus. RESULTS: Significant neuronal apoptosis was observed in the Seizure group and peaked at 24 hrs, with an apoptosis rate of 12.54%±4.99%, compared with (2.24%±0.57%) in the Normal control group (P<0.001). The activity of NF-κB was detected at 6 hrs following seizure induction, and increased to maximal expression at 24 hrs (32.30±4.71/gcs)in the Seizure group. NF-κB activation was not found in the Normal control group. The PDTC pretreatment group showed a lower neuronal apoptosis rate and less NF-κB activity than the Seizure group. CONCLUSIONS: The activation of NF-κB may play important roles in the process of neuronal apoptosis following serious seizures. PDTC pretreatment could reduce the neuronal apoptosis, perhaps by inhibiting the expression of NF-κB.