Abstract: Objective To explore the effects and possible neural mechanisms of naloxone on learning and memory ability in rats with repeated febrile seizures (FS). Methods The warm water was adopted to induce rats FS model and to induce 21-days-old SD rats seizure one time every day, continuous up to 10 times.The rats were injected intraperitoneally with naloxone (1 mg/kg)immediately after FS occurred in naloxone-treated group(NT group, n=14), while the rats of FS-control group (FS group, n=14)were injected with equal volume 0.9% sodium chloride, the rats of normal-control group(NC group, n=12) were placed in 37℃ water about 5 minutes, then injected with equal volume sodium chloride.Latency, duration and grade of FS were observed and compared;step down test and step through test were used to detect short-term learning and memory ability;HE staining was adopted to observe the changes of histopathology in hippocampal neuron; Timm staining was used to observe mossy fiber sprouting (MFS) in hippocampus. Results 1)Seizure duration of NT group was shorter than that of FS group (P<0.05); seizure grade of NT group was significantly less than that of FS group (P<0.01);there was no significantly difference in seizure latency between two groups (P>0.05).2)Both step down test and step through test exhibited that the error times of FS group was at most, there were significant difference (P<0.01), but there were no significant difference (P>0.05) in NC group and NT group;after 24 hours, the step-down latency and step-though latency of FS group were obviously shorted, and had significant difference (P<0.05), there were also no significant difference (P>0.05) in NC group and NT group.3) HE staining showed that there were much lighter brain damage in NT group than in FS group.4) In FS-control group, Timm staining particle was significantly increased in the inner molecular layer of DG and stratum oriens of CA3 area, compared with NC group there had significant difference (P<0.01).Intervention with naloxone made it obviously decreased, compared with FS group significant difference could be seen(DG:P<0.01, CA3:P<0.05), but no significant difference compared with NC group (P>0.05). Conclusions Naloxone can lighten the brain damage resulted from repeated FS;Repeated FS can result in deficits of short-term learning and memory ability in rats, early intervention with naloxone can improve this recognition functional impairment;naloxone can degrade the degree of mossy fiber sprouting, this is one of possible neuromechanism of naloxone for improving cognitive dysfunction.

Key words: naloxone, febrile seizures, learning and memory, mossy fiber sprouting

摘要： 目的 探讨纳洛酮对反复热性惊厥大鼠近期学习记忆的影响及可能神经机制。方法 采用热水浴诱导大鼠惊厥模型, 诱导21 d SD大鼠每天惊厥1次, 连续10次, 纳洛酮干预组(NT组, n=14)每次惊厥发作后立即腹腔注射纳洛酮(1mg/kg), 惊厥对照组(FS组, n=14)腹腔注射等体积的生理盐水, 正常对照组(NC组, n=12)置于37℃水浴中5 min后腹腔注射等体积生理盐水。观察惊厥发作潜伏期、级别和持续时间的差异;采用跳台和避暗试验测试近期学习记忆能力;HE染色观察海马神经元形态学改变;Timm染色观察海马苔藓纤维发芽状况。结果 1)NT组较FS组惊厥持续时间明显缩短(P<0.05), 级别显著降低(P<0.01), 而发作潜伏期两组差异无统计学意义(P>0.05);2) 跳台及避暗实验, FS组错误次数明显增多(P<0.01), 而NC组与NT组相比差异无统计学意义(P>0.05);24 h记忆成绩, FS组跳台及步入潜伏期明显缩短(P<0.05), 而NC组与NT组相比差异无统计学意义(P>0.05);3)HE染色显示NT组较FS组脑损伤的程度轻;4)Timm染色显示FS组DG区及海马CA3区Timm染色颗粒明显增加(P<0.01);NT组与FS组相比Timm染色颗粒明显减少(DG区P<0.01, CA3区P<0.05), 而NC组与NT组相比差异无统计学意义(P>0.05)。结论 纳洛酮可减轻惊厥性脑损伤;可改善多次FS发作后的近期学习记忆能力减退, 降低海马苔藓纤维发芽程度, 这可能是纳洛酮改善反复FS后认知功能障碍的神经机制之一。

关键词: 纳洛酮, 热性惊厥, 学习记忆, 苔藓纤维发芽