孕期吸入异氟醚对子代大鼠认知功能及海马GAP-43和NPY表达的影响

目的:探讨大鼠孕期吸入异氟醚对子代认知功能以及海马生长相关蛋白-43(GAP-43)和神经肽Y(NPY)表达的影响。方法:选取孕龄为18 d的SD大鼠12只,随机分为异氟醚处理组和对照组(n=6)。异氟醚组使用1.3%的异氟醚处理6 h,对照组吸入含30%氧气的空氧混合气体。待幼鼠出生4周后,使用水迷宫实验,检测幼鼠空间学习记忆能力。测试结束后,取其海马组织行免疫组织化学染色,观察GAP-43和NPY在两组仔鼠海马CA1区表达的差异。结果:在水迷宫测试中,与对照组仔鼠相比,异氟醚组仔鼠平均逃逸潜伏期时间明显延长(P<0.05)、第三象限活动时间和穿越平台次数明显减少(P<0.05)。异氟醚组仔鼠海马CA1区神经细胞内GAP-43和NPY的表达均较正常对照组明显下降,差异有显著性意义(P<0.01)。结论:1.3%异氟醚处理孕18 d的大鼠6 h可导致仔鼠学习记忆功能降低,这可能与海马CA1区GAP-43和NPY表达下调有关。

Effects of gestational isoflurane exposure on postnatal memory and learning in rats

Objective: To investigate the effects of gestational isoflurane exposure on postnatal memory and learning and growth-associated protein-43(GAP-43),neuropeptide Y(NPY) expression in the hippocampus of pups. Methods: Twelve maternal Sprague-Dawley rats at gestation d 18(E18) were randomly divided into isoflurane group(n=6) and control group(n=6).Rats in isoflurane group were exposed to 1.3%isoflurane for 6 h.For control group,animals breathed in 30% oxygen and air mixed gas at the same condition.Spatial learning and memory of the offspring were determined with the Morris Water Maze(MWM) after postnatal 4 weeks.The changes of GAP-43 and NPY expression in the hippocampal CA1 region of the pups were determined by immunohistochemistry. Results: In MWM training,the escape latency to platform of the pups in isoflurane group was significantly longer,and the time spent in the third quadrant and times of original platform crossing were less than those of control animals(P<0.05).The number and optical density of GAP-43 and NPY positive neurons in the hippocampus of pups decreased significantly in the isoflurane group compared with the controls(P<0.01). Conclusion: Isoflurane exposure in pregnant rats significantly impaires the spatial memory and learning of their pups at a juvenile age,which may be associated with the down-regulation of GAP-43 and NPY in the hippocampus.