妊娠大鼠吸入异氟烷或七氟烷对幼鼠学习记忆能力的影响

Effects of isoflurane or sevoflurane inhalation in pregnant rats on learning and memory abilities of young rats

目的研究妊娠大鼠吸入异氟烷、七氟烷对幼鼠学习记忆能力及海马丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法将SPF级、雌性SD大鼠25只,随机分为对照组(C组)、妊娠前吸入异氟烷组(BI组)、妊娠期吸入异氟烷组(PI组)、妊娠前吸入七氟烷组(BS组)和妊娠期吸入七氟烷组(PS组),每组各5只。BI组和BS组分别吸入1.6%异氟烷和2.4%七氟烷6 h,苏醒后合笼;PI组和PS组正常合笼后,于妊娠第6,10,14和18 d分别吸入1.6%异氟烷和2.4%七氟烷6 h;对照组正常合笼,且不进行任何干预。用Morris水迷宫实验检测14 d幼鼠的学习记忆能力。结果C组、BI组、BS组、PI组与PS组幼鼠定位航行实验第5天的逃逸潜伏期分别为(34.11±2.56),(35.06±2.71),(33.89±3.02),(47.39±5.11),(40.42±4.15)s;穿越原平台的次数分别为(6.21±2.53),(5.96±2.45),(6.07±2.41),(1.12±0.28),(2.87±0.62)次;空间探索时间分别为(35.78±6.11),(33.92±5.84),(34.73±6.02),(16.56±4.63),(20.32±4.81)s。定位航行实验第1~5天,5组幼鼠的逃逸潜伏期均逐渐缩短;与C组比较,PI组与PS组幼鼠第1~5天的逃逸潜伏期均明显延长,且PS组短于PI组;穿越原平台的次数明显减少,且PS组多于PI组;空间探索时间明显缩短,PS组长于PI组;PI组与PS组幼鼠海马组织p-ERK1/2蛋白相对表达量明显降低,PS组高于PI组;海马组织PKCα蛋白相对表达量明显升高,且PS组低于PI组(均P<0.05)。结论妊娠大鼠于妊娠6,10,14和18 d暴露于1.6%异氟烷或2.4%七氟烷,可使14 d幼鼠的学习记忆能力降低,且异氟烷的作用较七氟烷更强,其作用机制可能与调控幼鼠海马组织MAPK通路的信号转导相关。

Objective To investigate the effects of isoflurane and sevoflurane inhalation in pregnant rats on learning and memory ability and hippocampal mitogen-activated protein kinase(MAPK)signaling pathway in young rats.Methods Twenty-five female SPF rats were randomly divided into control group(C group),isoflurane group before pregnancy(BI group),isoflurane group during pregnancy(PI group),sevoflurane group before pregnancy(BS group)and sevoflurane group during pregnancy(PS group),with 5 rats in each group.BI group and BS group inhaled 1.6%isoflurane and 2.4%sevoflurane for 6 h,and were mated after waking up;PI group and PS group inhaled 1.6%isoflurane and 2.4%sevoflurane for 6 h on the 6th,10th,14th and 18th d of pregnancy after the normal mated,respectively;C group was mated normally without any intervention.Morris water maze experiment was used to test the learning and memory ability of young rats at 14 d.Results The escape latency of the C,BI,BS,PI and PS groups on the 5th d of the positioning experiment were(34.11±2.56),(35.06±2.71),(33.89±3.02),(47.39±5.11),(40.42±4.15)s;the times of crossing the original platform were(6.21±2.53),(5.96±2.45),(6.07±2.41),(1.12±0.28)and(2.87±0.62)times;the space exploration time were(35.78±6.11),(33.92±5.84),(34.73±6.02),(16.56±4.63),(20.32±4.81)s.From 1-5 days of the positioning experiment,the escape latency of the 5 groups of young rats were gradually shortened.Compared with C group,the escape latency of the young rats in PI group and PS group were significantly prolonged from 1-5 days,and PS group was shorter than PI group;the number of crossings of the original platform were significantly reduced,and PS group was more than PI group;the space exploration time were significantly shortened,PS group was longer than PI group;the relative expression of p-ERK1/2 protein in hippocampus tissues were significantly reduced in PI group and PS group,and PS group was higher than PI group;the relative expression of PKCαprotein in hippocampus tissues was significantly increased,and PS group was lower than PI group(all P<0.05).Conclusion Pregnant rats exposed to 1.6%isoflurane or 2.4%sevoflurane on the 6th,10th,14th and 18th d of pregnancy can reduce the learning and memory abilities of young rats at 14 days,and the effect of isoflurane is better than that of sevoflurane,and the mechanism may be related to the signal transduction of MAPK pathway in hippocampus of young rats.