摘要
目的探讨孕期小鼠多次氯胺酮暴露对子代胎鼠成年后学习记忆功能的影响及小胶质细胞变化。方法孕鼠12只,随机分为两组:对照组(Ctrl组,n=6)与氯胺酮组(Ket组,n=6)。Ket组孕鼠于孕12.5(E12.5)天予以腹腔注射氯胺酮120 mg/kg,每天一次,连续注射5天;Ctrl组给予腹腔注射等体积的生理盐水。连续给药结束后第二天(即E17.5),每组随机选取3只孕鼠剖宫取胎行荧光免疫学检测观察胎鼠某些脑区小胶质细胞标记物Iba-1的表达变化;其余3只孕鼠待其自然分娩后,子代小鼠饲养至成年(8周),随机选取12只行Morris水迷宫检测,观察成年后两组子代小鼠的逃避潜伏期、穿越平台的次数以及目的象限活动时间变化来反映对学习记忆能力的影响。结果 Ket组孕鼠多次氯胺酮给药后,胎鼠下丘脑区标记的小胶质细胞数目增多(P<0.05),而海马区、脑室下区及前额叶皮质区Iba1标记小胶质细胞数目无明显变化。与Ctrl组相比,Ket组逃避潜伏期延长、穿台次数减少、目的象限活动时间明显缩短(P<0.05)。结论孕鼠多次腹腔注射氯胺酮可引起子代小鼠成年后学习记忆功能障碍,下丘脑区小胶质细胞可能参与氯胺酮所致的学习记忆障碍。
Objective To investigate the effect of multiple ketamine exposure in pregnant mice on learning and memory function in adult offspring and its related mechanism. Methods Pregnant mice was intraperitoneally injected with ketamine（ 120 mg/kg） once a day,consecutively for 5 days from embryonic day 12. 5（ E12. 5） to E16. 5（ n = 6）. Control mice received same volume of saline（ n = 6）. Three pregnant mice in each group were randomly selected to collect the fetus mice at E17. 5. The brains of fetus mice were rapidly removed,fixed. Immunofluorescence was performed to detect the expression of microglial marker Iba-1 in the different brain areas of fetal mice. The rest of the pregnant mice gave birth to pups which were then raised to adulthood（ 8 weeks）,12 of those pups were randomly selected for Morris water maze test. Results The number of Iba-1 positive cells increased in the hypothalamus of fetal mice at E17. 5 after intraperitoneal injections of ketamine in pregnant mice（ P 〈 0. 05）. Multiple injections ketamine of pregnant mice with fetus mice from E12. 5 to E16. 5 led to the learning and memory deficit in adult offspring manifested with longer escape latency,less times of crossing the platform and less time spent in the target quadrant（ P 〈 0. 05）. Conclusion Maternal multiple exposures of ketamine leads to the learning and memory dysfunction in adulthood of offspring mice; microglia in the hypothalamus of the embryonic mice may be involved in this impairment.
出处
《临床和实验医学杂志》
2018年第4期340-343,共4页
Journal of Clinical and Experimental Medicine
