中文摘要：

目的探索幼年SD大鼠不同程度脱髓鞘对惊厥易患性的影响。方法选用21d幼鼠181只，按随机数字表法分为对照组和实验组，对照组给予正常饲料喂养2周（n=41）及4周（n=45），实验组给予含0．6％铜宗的饲料分别喂养2周（n=48）及4周（n=47）制备脱髓鞘模型。通过免疫组织化学及蛋白质印迹检测髓鞘碱性蛋白（MBP）含量，对脱髓鞘模型进行鉴定；利用匹罗卡品诱导大鼠惊厥发作，记录其出现惊厥的时间；膜片钳记录自无镁人工脑脊液（ACSF）诱导后海马脑片自发放电的潜伏期；利用视频-脑电图检测大鼠行为及其脑电图的改变；采用原位末端标记法（TUNEL法）观察海马神经元凋亡情况。结果免疫组织化学及蛋白质印迹检测结果显示，铜宗可导致海马及其胼胝体内髓鞘脱失，且铜宗4周组大鼠髓鞘脱失程度明显重于铜宗2周组。铜宗4周组大鼠经匹罗卡品诱发惊厥的潜伏期[（13．33±3．46）min]较其同龄对照组[（19．66±4．33）min]明显缩短（t=4．62，P〈0．01）；膜片钳测定结果发现，铜宗2周组大鼠自发放电潜伏期[（35．00±5．03）min]与同龄对照组[（49．86±10．65）min]相比明显缩短，差异有统计学意义（t=3．34，P〈0．05）；铜宗4周组与其同龄对照组相比，大鼠自发放电的潜伏期（min）亦明显缩短[19．29±3．95与51．86±10．79，t=7．50，P〈0．01]，且较铜宗2周组缩短更为明显（t=6．50，P〈0．01）；通过视频及脑电图联合检测发现，7／11的铜宗2周组大鼠脑电图出现了癫痫样放电，铜宗4周组出现异常脑电图阳性率达10／10，同龄对照组脑电图均无异常；铜宗2周及4周组海马神经元TUNEL阳性细胞数与对照组相比，差异均无统计学意义。结论幼年大鼠脱髓鞘后，惊厥易患性明显增加，且脱髓鞘程度越重，惊厥潜伏期缩短更为明显，提示髓鞘的病变有可能是导致癫

英文摘要：

Objective To evaluate the effect of cuprizone-induced demyelination on seizure susceptibility in immature rats. Methods Demyelination model was induced in 21 d immature rats fed with 0.6% cuprizone （CPZ） for 2 weeks （CPZ 2 weeks group） and 4 weeks （CPZ 4 weeks group）. Morphological changes of myelinated fibers were examined using Gallyas staining. The expression of myelin basic protein （MBP） was determined by immunohistochemistry and western blot. The latency of seizure in CPZ rats induced by piloearpine and the latency of spontaneous of discharge in hippocampus slices induced by Mg^2＋ free artificial cerebrospinal fluid （ACSF） were determined. In addition, behavior and epileptiform spikes were recorded by video-electroencephalogram monitoring. The apoptosis cells in hippocampus of rats were detected by TdT-mediated dutp nick end labeling （TUNEL）. Results The results showed that myelinated fibers of the CPZ group were degenerated, and with significantly decreased MBP expression, related to control group rats. Besides, the MBP expression was decreased significantly in CPZ 2 weeks group compared to that of rats in CPZ 4 weeks group. The latency of seizure induced by pilocarpine was decreased in CPZ 4 weeks group（ （ 13.33 ± 3.46） min） related to that in control group （ （ 19. 66 ± 4. 33 ） min, t =4. 62,P 〈 0.01 ）. In addition, the latency induced by Mg^2＋ free ACSF in hippocampus slice was significantly decreased in CPZ 2 weeks group （ （ 35.00 ± 5.03 ） min vs （49. 86 ± 10. 65 ） min, t = 3.34, P 〈 0. 05） and CPZ 4 weeks group（ （ 19.29 ± 3.95） min vs （51.86 ± 10.78） min, t = 7.50, P 〈 0.01 ）. While no spontaneous epileptiform spikes were observed in control group, abnormal discharge can be seen in 7/11 of CPZ 2 weeks rats and 10/10 of CPZ 4 weeks rats. Finally, there was no difference in the numbers of apoptosis cells in hippocampus between CPZ groups and control groups. Conclusions Immature rats treated with CPZ show increased seizure susc