艾芬地尔预处理对七氟醚导致的幼年大鼠学习记忆和认知能力损伤的保护作用及机制

Protective effects of pretreatment with ifenprodil on learning,memory and cognitive dysfunction induced by sevoflurane in neonatal rats

目的观察N-甲基-D-天冬氨酸亚型受体(NR2B)选择性拮抗剂艾芬地尔对七氟醚导致的幼年大鼠学习、记忆和认知能力损伤的保护作用及机制。方法 SD大鼠28只,7日龄,体重15~18g,采用随机数字表法,将大鼠分为四组,每组7只:对照组(C组),腹腔注射生理盐水0.2 ml;艾芬地尔组(I组),腹腔注射N-甲基-D-天冬氨酸(NMDA)亚型受体NR2B选择性拮抗剂艾芬地尔5.0mg/kg;七氟醚组(S组),吸入七氟醚前2h腹腔注射生理盐水0.2ml,持续吸入2.0%七氟醚4h;艾芬地尔+七氟醚组(IS组),对应时点腹腔注射艾芬地尔5.0 mg/kg,持续吸入2.0%七氟醚4h。给药后3周处死大鼠,取其海马切片,行电生理实验,在Schaffer侧支上给予高频成串刺激(100Hz,4个脉冲),待值群峰电位(population spike,PS)稳定后,每隔10分钟检测单通道刺激后值群峰电位振幅(population spike amplitude,PSA)值和记录长时程增强(long-term potentiation,LTP),诱发成功情况。结果与C组比较,在单通道刺激后各时点S组PSA值明显减小,LTP诱发成功率明显降低(P<0.01);与S组比较,在单通道刺激后各时点IS组PSA值明显增大,LTP诱发成功率明显升高(P<0.01)。结论 NR2B受体参与七氟醚导致的新生大鼠认知功能障碍,艾芬地尔5.0mg/kg预处理有助于改善其神经毒性,产生脑保护作用。

Objective To evaluate the role and mechanism of ifenprodil,which is the selective antagonist of N-methyl-D-aspartic acid subtype receptor NR2 B,in soflurane-induced cognitive dysfunction in neonatal rats.Methods Twenty-eight 7-day-old Sprague Dawley rats,weighing 15-18 g,were randomly divided into 4 groups（n=7each）：control group（group C）,ifenprodil group（group I）,sevoflurane group（group S）and ifenprodil＋sevoflurane group（group IS）.Normal saline 0.2ml was injected intraperitoneally in group C.Specific NR2B receptor antagonist ifenprodil 5 mg/kg was injected intraperitoneally at the corresponding time points in group I.Normal saline 0.2ml was injected intraperitoneally and 2.0% sevoflurane was inhaled for 4hin group S.Ifenprodil 5mg/kg was injected intraperitoneally 2h before sevoflurance inhalation,and 2.0% sevoflurance was inhaled for 4h in group IS.The rats were then sacrificed 3weeks after administration,their brains were immediately removed and hippocampal slices were prepared for electrophyisological experiments.The value of population spike amplitude（PSA）and long-term potentiation（LTP）were measured every 10 minutes.Induced LTP was recorded.Results Compared with group C,the values of PSA and rates of induced LTP were significantly decreased in group S（P〈0.01）.The values of PSA and rates of induced LTP were significantly increased in group IS than those in group S（P〈0.01）.Conclusion NR2B receptor is involved in sevoflurance-induced cognitive dysfunction in the neonatal rats.Pretreatment with ifenprodil 5.0mg/kg can improve the neurotoxicity and protect the brain.