纳洛酮对反复高热惊厥后神经细胞凋亡的影响

目的　探讨不同用药时间的纳洛酮对反复高热惊厥后神经细胞凋亡的影响。方法　利用热水浴惊厥模型隔日诱导 70只生后 15dSD大鼠发生 7次热惊厥 ,期间治疗组大鼠每次惊厥发作后分别于 5、30、6 0min ,2h腹腔注射 1mg/kg纳洛酮 ,而惊厥对照组大鼠上述时点腹腔注射等量生理盐水。末次惊厥后 2 4h处死大鼠 ,采用原位末端脱氧核苷酸生物素标记 (TUNEL)法分别测定大鼠海马结构及大脑皮层神经元凋亡情况 ;并应用透射电镜观察凋亡细胞超微形态学改变。结果　与惊厥对照组比较 ,大鼠热惊厥后 5、30、6 0min应用纳洛酮均可明显减少神经细胞凋亡 (P <0 .0 1) ;而惊厥后 2h给药 ,神经细胞凋亡率差异无显著性 (P >0 .0 5 )。惊厥后不同时间给药组间比较 ,发现TUNEL阳性细胞数有显著差异 (P <0 .0 5 ) ,提示纳洛酮愈早应用 ,凋亡发生愈少。结论　早期应用纳洛酮可明显减少高热惊厥脑损伤后神经细胞凋亡 ,从而有效地保护神经细胞

Effect of naloxone on neuronal cells apoptosis induced by repeated febrile seizures

Objective To investigate the effect of naloxone on neuronal cells apoptosis induced by repeated febrile seizures(FS).Methods Warm water was used to induce 70 rats FS model 15 days after birth in this study; each rat was induced 7 times febrile seizures at one- day interval . Seventy rats were randomly divided into naloxone-treated group and FS control group, receiving injection of naloxone or saline at 5, 30, 60 min and 2 hours after FS each day respectively. The rats were sacrificed 24 hours after the last seizure. Neuronal cell apoptosis was determined by TUNEL methods in situ cell death kit. TUNEL positive cells(TPC) were stained and counted as apoptosis in hippocampus and cortex. Ultrastructural changes of apoptosis neurons were observed under the electron microscope(EM). Results Compared with the FS control group, naloxone treatment could significantly relieve neuron apoptosis induced by repeated FS when it was used at 5, 30, 60 min after the last FS. However there was no significant difference in neuron apoptosis between 2 groups when naloxone was used at 2 hours after FS. The comparison of different naloxone administration time showed that the earlier naloxone was injected,the fewer apoptosis neurons were induced by FS.Conclusion Naloxone,as early used in proper dosage,may significantly alleviate apoptosis after repeated FS ,and protect neurons.