纳洛酮对幼年大鼠反复热惊厥后远期惊厥易感性的影响

Effect of naloxone on remote seizure susceptibility

目的 :探讨纳洛酮对幼年大鼠反复热惊厥后远期惊厥易感性的影响。方法 :用热水浴惊厥模型诱导生后1 5d的SD大鼠发生 7次热性惊厥 ,期间两治疗组大鼠 (各 1 3只 )每次惊厥一出现立即腹腔注射低剂量纳洛酮 (分别为1mg/kg和 2mg/kg) ,而惊厥对照组大鼠 (n =1 3)仅腹腔注射相同体积的生理盐水。间隔 2个月再热水浴 1次 ,观察比较治疗组和惊厥对照组大鼠远期惊厥发生率、惊厥潜伏期、惊厥持续时间及惊厥程度的差异。采用Timm染色观察神经元海马齿状回苔藓纤维发芽状况。结果 :未接受纳洛酮治疗的有幼年反复热性惊厥史的对照组大鼠 ,2个月后再次接受热刺激时 ,惊厥发生率为 84 .6 % ,惊厥潜伏期 (3.6 5± 0 .77)min ,惊厥持续时间 (2 1 .1 8± 4 .0 6 )min ,惊厥级别评分 (4 .5 4± 0 .78) ,5级惊厥发生率达 6 9.3% ,且有 2只大鼠出现惊厥持续状态 ,其中 1只抽搐后死亡 ;而接受纳洛酮治疗的实验组大鼠 ,2个月后再次接受热刺激时 ,惊厥发生率、惊厥潜伏期、惊厥持续时间、惊厥级别评分分别为5 7.7%、(3.78± 0 .6 9)min、(5 .6 6± 2 .78)min、(2 .97± 1 .1 8) ,5级惊厥发生率仅为 1 9.3% ,无 1只出现惊厥持续状态。比较两组惊厥发生率、惊厥潜伏期差异均无显著性 ,但惊厥持续时间、惊厥级别评分。

Objective : To evaluate the effect of low dose naloxone on remote seizure susceptibility after repeated febrile seizures(FS) in developing age. Methods: Warm water induced rat FS model was developed in this study.Forty nine SD rats were randomly divided into two groups: normal control group( n =10) and hyperthermic seizure group( n =39).The latter was further divided into FS control group( n =13) and naloxone treated group( n =26). The dose of naloxone was different in the two naloxone treated groups(13/each group). One group dose was 1 mg/kg, and the other 2 mg/kg. Each rat of hyperthermic seizure groups was induced to have 7 febrile seizures at the interval of 1 day. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone treated group, while the rats of other groups were injected with 0.9% sodium chloride. After the seventh stimulation, all rats were left un stimulated for 2 months, then re stimulated. Re stimulated seizureincidence rate, seizure duration and seizure grade in different groups were observed and compared with each other. Hippocampal mossy fiber sprouting was detected by Timm stain. Results: In naloxone treated group, the rats'seizure duration and seizure grade [(5.66±2.78) min,(2.97± 1.18)] significantly decreased ( t =5.035, P < 0.01; t =3.343 , P <0.01) compared with those in FS control group[(21.18±4.06) min, (4.54± 0.78)], although no significant gap was observed on seizure incidence rate(57.7%,84.6% respectively) and seizure latency between them. In non treated group,in which two rats developed status epilepsy, the incident rate of the fifth grade seizure was 69.3%, much higher than 19.3% of naloxone treateded group. Timm stain pattern showed that the straining in the IML(inner molecular layer) of treated group rats was much lighter than that of non treated group[(2.33±1.03), (0.92±0.79 ), P <0.01].Conclusion: Low dose naloxone used on naive rat with repeated febrile seizures can efficiently decrease the seizure susceptibility in the mature period,and lighten the neural damage by twice hit seizure in the mature period as well.