国际麻醉学与复苏杂志   2018, Issue (11): 0-0
    
艾芬地尔对异氟醚麻醉后学习记忆损害的影响
张朋, 许芳霞, 崔银, 宋佳, 刘欢, 顾小萍1()
1.南京大学医学院附属鼓楼医院
Effects of ifenprodil on isoflurane-induced impairment of learning and memory
 全文:
摘要：

目的　探讨侧脑室给予N-甲基-D-天冬氨酸2B（N-methyl-D-aspartate receptor subunit 2B， NR2B）受体拮抗剂艾芬地尔对长时程异氟醚麻醉后小鼠学习记忆损害的影响。　方法　雄性C57BL/6小鼠80只，8周龄，按随机数字表法分为5组（每组16只）：空白对照组（C组），吸入O2维持6 h；假手术组（S组），侧脑室注射生理盐水2 μl后吸入O2维持6 h；异氟醚组（A组），侧脑室注射生理盐水2 μl后吸入1.3%的异氟醚维持6 h；异氟醚+艾芬地尔组（AI组），侧脑室注射艾芬地尔（2 μg）2 μl后吸入1.3%的异氟醚维持6 h；艾芬地尔组（I组），侧脑室注射艾芬地尔（2 μg）2 μl后吸入O2维持6 h。用新物体识别实验（novel object recognition， NOR）和场景恐惧实验（fear conditioning， FC）检测麻醉后第3、7天小鼠的学习记忆。用实时荧光定量聚合酶链式反应（quantitative real time polymerase chain reaction， q-PCR）检测海马NR2B mRNA表达情况。　结果　在NOR中，麻醉后第3天和第7天，与S组比较，A组辨别指数下降（P<0.05）；与A组比较，AI组辨别指数升高（P<0.05）。在FC中，麻醉后第3天和第7天，与S组比较，A组凝滞时间百分数减少（P<0.05）；与A组比较，AI组凝滞时间百分数增加（P<0.05）。q-PCR结果显示，麻醉后即刻，与S组比较，A组海马NR2B mRNA表达升高（P<0.05）；麻醉后第3天和第7天，与S组比较，A组海马NR2B mRNA表达降低（P<0.05）；与A组比较，AI组海马NR2B mRNA表达升高（P<0.05）；麻醉后即刻、第3天和第7天，与S组比较，I组海马NR2B mRNA表达降低，但差异无统计学意义（P>0.05）。　结论　侧脑室预给予艾芬地尔可减轻长时程异氟醚麻醉后小鼠学习记忆损害，其机制可能与海马NR2B表达改变有关。
关键词： 异氟醚；　学习记忆损害；　艾芬地尔；　N-甲基-D-天冬氨酸2B受体
Abstract:

Ｏｂｊｅｃｔｉｖｅ　To investigate the long-term effects of intracerebroventricular administration of ifenprodil, a N-methyl-D-aspartate receptor subunit 2B(NR2B) receptor antagonist, on isoflurane-induced impairment of learning and memory in mice.　Methods　Eighty male C57BL/6 mice (8 weeks old) were randomly divided into five groups (n=16): mice in control group (group C) inhaled O2 for 6 h. Those in sham group (group S) inhaled O2 for 6 h after intracerebroventricular injection of 2 μl NS. Those in isoflurane group (group A) inhaled 1.3% isoflurane for 6 h after intracerebroventricular injection of 2 μl NS. Those in isoflurane + ifenprodil group (group AI) inhaled 1.3% isoflurane for 6 h after intracerebroventricular injection of 2 μg ifenprodil (in 2 μl). Those in Ifenprodil group (group I) inhaled O2 for 6 h after intracerebro- ventricular injection of 2 μg ifenprodil (in 2 μl). The learning and memory of the mice 3 d and 7 d after anesthesia was examined by new object recognition (NOR) and contextual fear conditioning test (FC). NR2B mRNA expression in the hippocampus was semi-quantified with quantitative real time polymerase chain reaction(q-PCR).　 Results　Three and seven days after anesthesia, mice in group A showed decreased discrimination index for novel vs. familiar objects, compared with the group S (P<0.05). Compared with group A, group AI exhibited an increased discrimination index (P<0.05). Three d and 7 d after anesthesia, the percentage of freezing time in group A in FC significantly decreased (P<0.05), compared with that of group S. Compared with group A, group AI showed an increased percentage of freezing time (P<0.05). The q-PCR data showed that immediately after anesthesia, NR2B mRNA levels in the hippocampus were elevated in group A, compared with the group S (P<0.05). However, 3 d and 7 d after anesthesia, NR2B mRNA levels in the hippocampus reduced in group A, compared with group S (P<0.05). Compared with the group A, group AI had higher levels of NR2B mRNA in the hippocampus (P<0.05). Immediately or 3 d and 7 d after anesthesia, compared with group S, group I had lower levels of NR2B mRNA in the hippocampus, but there was no statistical significance (P>0.05).　Conclusions　Intracerebroventricular administration of ifenprodil before anaesthesia can decrease isoflurane-induced impairment of learning and memory in mice probably by reducing NR2B expression in the hippocampus.
Key words: Ifenprodil;　Impairment of learning and memory;　Ifenprodil;　N-methyl-D-aspartate receptor subunit 2B receptor