新生大鼠反复惊厥对海马区肾上腺皮质激素受体表达的影响

目的 研究新生期大鼠反复惊厥对海马区肾上腺皮质激素受体MR和GR表达的影响,以及对成年期大鼠记忆功能的影响,探讨发育期脑损伤和脑内相关受体之间的相互关系.方法 生后7 d的SD大鼠随机分成两组,每组40只,惊厥组每日吸入三氟乙醚诱导惊厥发作1次,每次持续30 min,连续6 d;于反复惊厥后1、3、7、30、60 d处死大鼠取脑,分别采用免疫组织化学方法观察大鼠海马肾上腺皮质激素受体MR和GR表达的变化.最后一组大鼠处死前于第61～65天行Morris水迷宫实验,检测大鼠的学习记忆功能.对照组同样操作但不吸入三氟乙醚.结果 61～64 d,两组大鼠寻找平台时间均逐渐缩短,惊厥组大鼠在第64天的平均寻找平台时间[(82 424.3±35 622.0)ms]与对照组[(40 712.4±29 467.6)ms]比较明显延长(P=0.001).在第65天,惊厥组大鼠120 s内穿越原平台位置次数[(1.2±0.9)次]较对照组[(3.1±1.3)次]明显减少(P<0.001).免疫组化结果显示新生大鼠反复惊厥后的1、3、7、30、60 d海马CA1～4区GR、MR的表达较埘照组明显降低(P<0.05).结论 海马区GR及MR随脑发育成熟表达不断增高,呈现一定规律及分布特点,参与了脑发育过程.新生大鼠反复惊厥造成海马GR、MR表达的持续异常,参与发育期脑损伤.

effects of recurrent neonatal seizures on expression of minerocorticoid receptor and glucocorticoid receptor in the rat brain

Objective Objective To investigate the effects of flurothyl -induced neonatal recurrent seizures on minerocorticoid receptor (MR) and glueocorticoid receptor (GR) expression in developing rat brain, and discuss the relationship between these receptors and developing brainhurt.Methods 80 of 7 -day -old (P7) Sprague -Dawley rats were divided randomly into two groups: the control group and the seizure group.Seizures were induced by inhalant flurothyl daily in six consecutive days.The brain was sampled on these time point(1,3,7,30,60 d).The expressions of minerocorticoid receptor and glucocorticoid receptor protein in dentate gyms andhippocampus were detected immuno -histochemistry method.On days 61 -64, rats were tested for spatial memory by using the Morris water maze task.Results On days 64, the escape latencies in water maze of the rats in the seizure group were significantly longer than those of the control rats [(42 424.3 ± 35 622.0) ms vs (40 712.4 ± 29 467.6)ms, P = 0.001].On days 65, the frequency of crossing target within 120s in water maze of the rats in the seizure group were significantly less than those of the control rats [(1.2 ± 0.9) vs (3.1 ± 1.3) , P<0.001].There was no difference in seizures threshold between two groups on days 75 [(1 486.6 ± 661.9) s vs (1 840.6 ± 647.9) s, P = 0.133].Compaired the control rots, the expression of GR,MR protein in seizure rats decreased significantly in the CAI ,CA2,CA4 region ofhippocampus at time point 1,3,7,30,60 d(P <0.05).Conclusion Recurrent seizures in neonatal rats modify GR ,MR expression in the gyrus dentate andhippocampus of rats, and cause long -term cognitive deficit.This phenomenon raised the possibility that abnormal GR, MR expression might play an important role in long-term cognitive deficit induced by early life recurrent seizures.