阿米洛利对复杂型热性惊厥的影响

Effect of amiloride on complex febrile seizures

目的观察阿米洛利对复杂型热性惊厥的作用及其可能机制。方法建立Sprague-Dawley(SD)幼鼠复杂型热性惊厥模型,将40只SD幼鼠分为正常对照组、热性惊厥组、阿米洛利两种剂量预处理组(1.3阿米洛利组和10阿米洛利组),每组10只。在热性惊厥发作过程中观察阿米洛利预处理对体温升高、发作潜伏期的影响,以及对热性惊厥后海马区星形胶质细胞数及白细胞介素1β(IL-1β)mRNA含量的影响。结果热性惊厥组于4.3~6.8 min体温达到39.5℃,1.3阿米洛利组和10阿米洛利组分别于8.3~10 min和9.3~11.6 min达到39.5℃,后两者体温达39.5℃的时间明显晚于热性惊厥组(P<0.01),且1.3阿米-洛利组和10阿米洛利组间有显著性差异(P<0.05)。1.3阿米洛利组发作潜伏期为10.67~14.50 min,体温阈值为41.3~42.1℃,10阿米洛利组潜伏期为12.33~16.60 min,体温阈值为41.4~42.1℃,而热性惊厥组潜伏期为7.67~9.50分钟,体温阈值为41.0~41.7℃,1.3和10阿米洛利两组潜伏期较热性惊厥组明显延长,并且全身强直发作的体温阈值明显高于热性惊厥组(P<0.01),阿米洛利高低剂量组间有明显差异(P<0.05)。阿米洛利预处理组星形胶质细胞较正常对照组增多,而较热性惊厥组明显减少(均P<0.01)。阿米洛利预处理组IL-1βmRNA含量明显少于热性惊厥组(P<0.01)。结论阿米洛利可抑制复杂型热性惊厥发作,具有一定的抗热性惊厥作用,这可能与抑制星形胶质细胞增殖、抑制炎性因子生成有关。

Objective To investigate the effect of amiloride on complex febrile seizures and the possible mechanism.Methods Young Sprague-Dawley（ SD） rats were used to establish a model of complex febrile seizures. A total of 40 young SD rats were divided into normal control group,febrile seizure group,amiloride pretreatment groups（ at doses of 1.3 and 10 mg/kg,respectively）,with 10 rats in each group. The effect of amiloride pretreatment on the increase in body temperature and latency period of seizures was observed during febrile seizures,as well as its effect on the number of astrocytes and the mRNA expression of interleukin-1β（ IL-1β） in the hippocampus.Results In the febrile seizure group,the body temperature reached 39. 5° C in 4. 3-6. 8 minutes,and in the 1. 3 and 10 mg/kg amiloride pretreatment groups,the body temperature reached 39.5° C in 8.3-10 and 9.3-11.6 minutes,respectively,suggesting that the latter two groups had a significantly longer time for body temperature to reach 39.5°C than the former group（ P〈0.01）; there was also a significant difference between the 1.3 and 10 mg/kg amiloride pretreatment groups（ P〈0.05）. The 1.3 mg/kg amiloride pretreatment group had a latency period of seizures of 10.67-14.50 minutes and a threshold of body temperature of 41.3-42.1°C,and the 10 mg/kg amiloride pretreatment group had a latency period of seizures of 12.33-16.60 minutes and a threshold of body temperature of 41.4-42.1°C; the febrile seizure group had a latency period of seizures of 7.67-9.50 minutes and a threshold of body temperature of 41.0-41.7°C. Compared with the febrile seizure group,the 1.3 and 10 mg/kg amiloride pretreatment groups had a significant increase in the latency period of seizures and a significantly higher threshold of body temperature（ P〈0.01）; there were also significant differences in the latency period of seizures and threshold of body temperature between the two amiloride pretreatment groups（ P〈0. 05）. The amiloride pretreatment groups had a significant increase in the number of astrocytes compared with the normal control group and a significant reduction compared with the febrile seizure group（ both P〈0. 01）. The amiloride pretreatment groups had significantly lower mRNA expression of IL-1β than the febrile seizure group（ P〈0. 01）. Conclusions Amiloride can prevent complex febrile seizures,possibly by inhibiting the proliferation of astrocytes and the production of inflammatory cytokines.