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目的:探讨银杏内酯B(GKB)对癫痫大鼠海马中Notch-1与低氧诱导因子-1α(HIF-1α)的影响。方法:21 d SD大鼠随机分为5组:生理盐水组(NS组)、戊四氮(PTZ)致癫痫持续状态(SE)模型组(PTZ组)、GKB治疗组(P+G组)、GKB治疗+Notch信号通路特异性抑制剂(DAPT)干预组(P+G+D组)、DAPT干预组(DAPT组)。1%PTZ(80 mg/kg)于大鼠腹腔注射诱导建立癫痫持续状态模型。建模前10 h大鼠海马注射DAPT(0.03 mg/kg),建模前30 min给予相关大鼠腹腔注射1 mg/ml GKB(5 mg/kg),各时间点未予药物组均给予等量生理盐水腹腔注射。NS、PTZ、P+G组建模后2、4、8、12、24、48和72 h,DAPT、P+G+D组建模后8 h分别取出大鼠海马组织,检测HIF-1α、Notch-1蛋白的含量和HIF-1α、Notch-1阳性细胞数的表达。结果:HIF-1α和Notch-1蛋白在NS组存在低水平表达,而且表达水平平稳;在PTZ组、P+G组存在明显的表达时程变化,2 h时表达开始上升,8 h表达达高峰,在各个时间点的表达与生理盐水比较差异明显(P<0.05)。在SE后8 h,PTZ组及P+G组大鼠海马内的HIF-1α和Notch-1蛋白表达水平和阳性细胞数表达较高,P+G组表达更高于PTZ组,而在DAPT处理后P+G组表达低于PTZ组(P<0.05)。结论:在癫痫持续状态后大鼠海马内的Notch和HIF-1α信号通路均被激活,银杏内酯B不仅进一步加强两个信号通路的表达,而且显示出Notch信号通路可能参与了海马内HIF-1α表达的调控。
Objective: To investigate the effect of ginkgolide B (GKB) on hippocampal Notch-1 and hypoxia-inducible factor-1α (HIF-1α) in epileptic rats. Methods: The 21 d SD rats were randomly divided into 5 groups: NS group, PTZ group, PTZ group, GKB treatment group (P + G group) , GKB treatment + Notch signaling pathway specific inhibitor (DAPT) intervention group (P + G + D group), DAPT intervention group (DAPT group). 1% PTZ (80 mg / kg) was intraperitoneally injected into rats to establish a model of status epilepticus. DAPT (0.03 mg / kg) was injected into the hippocampus of rats 10 h before modeling, and 1 mg / ml GKB (5 mg / kg) was intraperitoneally injected into the rats 30 min before modeling. The rats in each group were given no The amount of saline intraperitoneal injection. At 2, 4, 8, 12, 24, 48 and 72 h after NSC, PTZ and P + G groups were established, the hippocampal tissues of rats in DAPT and P + G + , The content of Notch-1 protein and the expression of HIF-1α, Notch-1 positive cells. Results: The expression of HIF-1α and Notch-1 protein in NS group was low and stable, and there was significant change in PTZ group and P + G group. The expression of HIF-1α and Notch- The peak at each time point was significantly different from that of saline (P <0.05). At 8 h after SE, the expression of HIF-1α and Notch-1 protein and the number of positive cells in hippocampus of PTZ group and P + G group were higher than that of PTZ group After treatment, the expression of P + G group was lower than that of PTZ group (P <0.05). CONCLUSION: Notch and HIF-1α signaling pathways are activated in rat hippocampus after status epilepticus. Ginkgolide B not only further enhances the expression of both signaling pathways, but also shows that Notch signaling pathway may be involved in the hippocampal HIF- 1α expression regulation.