纳洛酮对反复热惊厥脑损伤的干预作用

Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure

目的 探讨纳洛酮对反复高热惊厥致脑损伤的干预作用。方法 利用热水浴惊厥模型诱导生后 15天SD大鼠发生 7次热性惊厥 ,期间两治疗组大鼠每次惊厥一出现立即腹腔注射低剂量纳洛酮 1mg/kg和 2mg/kg ,而惊厥对照组大鼠仅腹腔注射相同体积的生理盐水 ,观察比较治疗组、惊厥对照组大鼠惊厥潜伏期、惊厥持续时间和惊厥发作程度的差异。采用HE染色观察大鼠海马神经元形态学改变 ;采用电镜观察海马神经元超微结构的损伤性变化。结果 惊厥对照组与纳洛酮治疗组大鼠比较 ,两者惊厥潜伏期差异无显著性 ,但惊厥持续时间 (t =5 5 0 8,P <0 0 1) ,惊厥级别评分(t=8 4 39,P <0 0 1)差异有显著性。HE染色及透射电镜的观察提示纳洛酮治疗组较惊厥对照组大鼠在细胞及细胞器水平惊厥性脑损伤的程度轻。结论 应用低剂量纳洛酮对反复热性惊厥的幼年大鼠进行干预治疗 ,虽然不能完全阻止惊厥的发生 ,但是可以保护脑细胞 。

Objective The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children So how to decrease the related damage is a very important issue The main purpose of the present study was to find out whether the non specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure induced brain damage Methods Warm water induced rat FS model was developed in this study Forty seven rats were randomly divided into two groups: normal control group ( n =10) and hyperthermic seizure groups ( n =37) The latter was further divided into FS control group ( n =13) and naloxone treated group ( n =24) The dose of naloxone is different in two naloxone treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone treated group, while the rats of the other groups were injected with 0 9% sodium chloride Latency, duration and grade of FS in different groups were observed and compared HE staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons Results In naloxone treated group, the rats′ FS duration and FS grade (5 02±0 63,2 63±0 72) were significantly lower( t =5 508, P <0 01; t =8 439, P <0 01) than those in FS control group(7 70±2 25 min, 4 52±0 49), although no significant gap was observed on FS latency between them In FS control group, HE staining pattern of hippocampal CA 1 and CA 2 showed lots of disordered neurons with confused polarity and vacuoles formed Nuclei were with various size, some rounded and some oblong While in naloxone treated groups, the arrangement of neurons was regular, only a small quantity of neurons had changed polarity and vacuoles formed Most nuclei were oblong and in the same size In hippocampal CA 1 region and dentate gyrus of rats from FS control group, EM showed that the most mitochondrion volumes obviously increased with vacuoles formed, the matrix condensed, the ridge obscured or disappeared, apoptosis body emerged Minor to moderate dilation of rough endoplasmic reticulum and Golgi′s complex was also observed However, in naloxone treated groups, the number of neurons with swollen mitochondrion and endoplasmic reticulum was much fewer than that in FS control group No apoptosis body was observed The comparison between them showed much lighter brain damage in naloxone treated groups than in FS control group Conclusion Although low dose naloxone could not totally stop the occurance of febrile seizure, it could lighten the brain damage resulted from repeated FS to some extent