新生期大鼠反复惊厥的实验研究  

Experimental research of recurrent seizures in neonatal rats

作　　者：王明欢[1] 菲娜薇 邓燕[3] 蒋犁 何农跃[3] 

机构地区：[1]浙江省宁波市妇女儿童医院新生儿重症监护室,315012 [2]江苏省南京市中大医院儿科,210009 [3]东南大学生物电子国家重点实验室,江苏省南京市210009

出　　处：《中华全科医学》2015年第4期520-522,567,共4页Chinese Journal of General Practice

基　　金：国家自然科学基金(81370739);2013江苏省自然科学基金(BK20131303)

摘　　要：目的建立用戊四氮(PTZ)制作的新生期大鼠反复惊厥发作的动物模型,并研究其行为学表现及远期结果。方法采用生后5 d(P5)的SD大鼠28只(随机分成实验组16只和对照组12只),予戊四氮腹腔注射连续给药5 d,每天观察实验动物的行为学变化,并在生后45 d用Y-型电迷宫测试大鼠的学习记忆能力,用尼氏染色和Timm染色法观察细胞形态学及苔藓纤维发芽的情况。应用SPSS 13.0软件进行2组均数的t检验,P<0.05定为差异有统计学意义。结果造模期,随着日龄增加,动物惊厥敏感性下降,但惊厥发作程度加重。生后45 d,实验组Y-型电迷宫测试中达到学会标准所需次数明显多于对照组(P<0.01),24 h记忆保持率明显低于对照组(P<0.01);Timm染色中,实验组大鼠的海马组织可见明显苔藓纤维发芽,而对照组则不明显(P<0.01);尼氏染色中2组均未见明显的神经元细胞坏死和丢失。结论新生期大鼠反复惊厥发作模型基本符合人类新生儿惊厥发作,可导致远期学习记忆能力下降,且有潜在的癫痫可能。本实验通过常用的致痫剂戊四氮制作新生期大鼠反复惊厥发作的动物模型,操作性强,重复性好,经济简便,为将来研究反复惊厥发作的新生儿提供了可靠的动物模型。Objective The animal models of recurrent seizure using neonatal SD rat induced by pentylenetetrazol（PTZ） was created. Their behavior in induced seizures ,long-term learning and memorizing abilities and staining result of hippocampus tissue were studied. Methods Twenty eight SD rats were randomly divided into two groups： the PTZ group （16 rats） and the control group（ 12 rats）. In the PTZ group, rats of the 5th day （postnatal 5 days, P5 ） were injected intraperitoneally with PTZ till seizure for 5 consecutive days（ from P5 to 1x））. While in the control group, P5 rats were injected saline of same dose and by the same way of injection,for 5 consecutive days. Their behavior was evaluated daily from P5 to P9. The learning and memorizing abilities were analyzed on P45 using the Y-type electric maze test. The cell morphology and the mossy fiber sprouting（MFS） in the rats＇ hippocampus tissue were analyzed by Nissl staining and Timm staining respectively on P45. Values are reported as mean ＋ SEM. SPSS13.0 software was used for statistical analysis. Single comparisons were tested using the t test,P 〈 0.05 was considered statistically significant. Results From P5 to P9, with the increase of age, the sensitivity to seizure-induction declined, but the condition of seizures aggravated. In the Y-type electric maze test, rats in PTZ group needed significantly more training times to learn the rule compared with those in the control group（ P 〈 0.01 ）, and were significantly lower the rate of 24-hour retention of memory than those in the control group （P 〈 O. 01 ）. There was no significant neuronal necrosis or loss in Nissl staining in neither groups, but significantly more MFS were observed in CA3 of the hippocampal tissue in PTZ group compared to the control group （ P 〈 0. 01 ）. Conclusion This model showed that recurrent seizures without cerebral parenchymal injury in neonatal infants may lead to not only the impairment of long-term learning and memorizing ability but also the t

关 键 词：新生期大鼠 反复惊厥 戊四氮 动物模型 苔藓纤维发芽 

分 类 号：R722.1[医药卫生—儿科] R3[医药卫生—临床医学]