摘要
目的:探讨拉莫三嗪(LTG)对围生期缺氧导致惊厥的新生大鼠(生后10 d)的神经保护作用。方法:新生大鼠随机分成缺氧-生理盐水组、缺氧-LTG组、常氧-生理盐水组和常氧-LTG组4组。缺氧-生理盐水组(n=26):用梯度缺氧方法制作急性缺氧模型(氧浓度低于4%),缺氧前0.5 h已腹腔注射生理盐水;缺氧-LTG组(n=26):腹腔注射LTG(20 mg.kg-1),0.5 h后放入同上的缺氧装置;常氧-生理盐水组(n=26):腹腔注射生理盐水后放入常氧浓度的相同装置;常氧-LTG组(n=26):腹腔注射LTG后放入同上的常氧浓度装置。尼氏染色评估惊厥发作1 h后及生后30 d大鼠的细胞丢失情况,Timm染色观察生后30 d大鼠的苔藓纤维发芽情况,戊四氮测量生后30 d大鼠的惊厥敏感性。结果:尼氏染色结果显示各组大鼠在惊厥发作1 h及生后30 d的两个时间点均未见明显神经元丢失。缺氧-LTG组在围生期缺氧惊厥的程度及敏感性与缺氧-生理盐水组无明显差异,常氧两组均未见惊厥发作。但在生后30 d,缺氧-LTG组大鼠对戊四氮的惊厥阈值较缺氧-生理盐水组明显增高(P<0.05),较常氧组降低(P<0.01),常氧两组间无差异(P>0.05)。缺氧-LTG组大鼠在生后30 d时,齿状回颗粒上层的苔藓纤维发芽分数较缺氧-生理盐水组明显降低(P<0.05),但与常氧两组间均无明显差异。结论:拉莫三嗪对围生期缺氧导致惊厥的大鼠有神经保护作用,降低了大鼠对化学致痫药物的敏感性,并且阻止了远期发展为癫痫的可能。
Objective： To investigate the possible neuroprotective effects of lamotrigine（LTG） on neonatal rats after hypoxia-induced seizures at postnatal day 10.Methods： Four groups of rats were studied at postnatal day 10.Rats in hypoxia-normal saline（NS） group（n=26） were subjected to acute hypoxia at postnatal day 10 according to the protocol of progressively decreasing oxygen（down to 4% O2） and intraperitoneally injected with NS half hour before hypoxia.Rats in hypoxia-LTG group（n=26） were subjected to acute hypoxia and received LTG（20 mg·kg-1） intraperitoneally half hour before hypoxia.Rats in normoxia-NS group（n=26） were injected with NS and placed in normal oxygen apparatus.Normoxia-LTG group（n=26） were injected with LTG and placed in normal oxygen apparatus.Nissl staining was performed to evaluate cell loss at one hour after onset of seizure and at postnatal day 30.Timm staining was performed to evaluate mossy fiber sprouting and seizure susceptibility was tested by pentylenetetrazol（PTZ） at postnatal day 30.Results： Nissl staining showed that there was no obvious neuronal loss after seizure induction at either postnatal day 10 or postnatal day 30 in all groups.The degree of seizure and seizure susceptibility of rats in hypoxia-LTG group was similar to that in hypoxia-NS group.The seizure threshold induced by PTZ of the rats in hypoxia-LTG group was significantly higher than that in hypoxia-NS group（P0.05） and lower than that in the two normoxia groups at postnatal day 30（P0.01）.There was no obvious difference between the two normoxia groups（P0.05）.Timm staining showed that supragranular zone of the dentate gyrus in hypoxia-LTG group was lower than that in hypoxia-NS group（P0.05）,but there was no obvious difference in the two normoxia groups at postnatal day 30.Conclusions： These results suggest that the potential neuroprotective effect of lamotrigine in these particular animal model of perinatal hypoxia-induced seizures.LTG decreased the long-term seizure susceptibility induced by chemical convulsant and prevented the later development of epilepsy.
出处
《东南大学学报（医学版）》
CAS
2010年第2期143-147,共5页
Journal of Southeast University(Medical Science Edition)
关键词
拉莫三嗪
新生大鼠
缺氧
惊厥
神经保护作用
苔藓纤维发芽
lamotrigine
neonatal rats
hypoxia
seizure
neuroprotective effects
mossy fiber sprouting
