国际麻醉学与复苏杂志   2016, Issue (2): 4-4
    
七氟醚对幼鼠海马组织神经元凋亡和γ-氨基丁酸A受体α1/α2亚型组成及远期空间探索能力的影响
谢思宁, 叶虹, 安立新, 李俊发1()
1.首都医科大学附属北京天坛医院麻醉科
The effects of sevoflurane on expression of protein Poly(ADP-ribose) polymerase-1 and γ-aminobutyric acid receptor α1/α2 in hippocampus and the adaptation ability of neonatal rats
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摘要:

目的 通过观察七氟醚对幼鼠海马组织多聚腺苷二磷酸核糖聚合酶-1 [Poly(ADP-ribose)polymerase-1,PARP-1]的表达、γ-氨基丁酸A受体(γ-aminobutyric acid subtype A receptor, GABAAR)α1/α2亚型组成及空间探索认知能力的影响,分析七氟醚对发育神经元的毒性作用及可能的相关机制。 方法 选取出生后7 d的SD幼鼠216只,设定0.8 MAC(2.11%)浓度七氟醚维持时间4 h作为麻醉处理条件。利用随机数字表法将幼鼠分为对照组(A组)、假麻醉组(B组)和麻醉组(C组),每组72只。经不同处理后3组分别于6、24、72 h各取6只幼鼠海马组织进行Western blot检测,确定PARP-1。再以同样方法、数量检测GABAAR α1亚型和α2亚型水平,观察GABAAR α1/α2亚型组成与神经元凋亡的关联。3组分别在幼鼠成长至5、8、14周时随机选12只进行旷场实验。 结果 与A组(100%)比较,C组于麻醉后6 h PARP-1表达水平明显增加[(216±15)%](P<0.05),而与A组(100%)比较,GABAAR α1/α2蛋白含量比值于麻醉结束后6 h[(126±6)%]、24 h[(127±8)%]及72 h[(183±22)%]均不同程度升高(P<0.05)。B组各检测指标与A组比较差异无统计学意义(P>0.05)。5周时接受七氟醚麻醉的幼鼠(C组)在旷场中平面活动及垂直活动均多于A组,B组各观察指标与A组比较差异无统计学意义(P>0.05)。8周和14周时,各组动物旷场表现差异无统计学意义(P>0.05)。 结论 七氟醚可引起早期的细胞死亡,且其神经毒性作用与受体的影响有关,可引起GABAAR α1/α2比值增加,α2亚型向α1亚型进行转化。七氟醚可引起成长中幼鼠在陌生环境中的活动增加,影响其短期内对新环境的适应能力及空间探索认知能力。

关键词: 七氟醚; 幼鼠; 多聚腺苷二磷酸核糖聚合酶-1; γ-氨基丁酸A受体; 认知
Abstract:

Objective To investigate the effect of sevoflurane on the expression of poly (ADP-ribose) polymerase-1(PARP-1) protein and γ-aminobutyric acid subtype A receptor(GABAAR) α1/α2 in hippocampus, and analyze its possible neurotoxicity mechanisms in the developing brain of rats. Methods Two hundred and sixteen neonatal SD rats (7 d postnatal, P7) were randomly divided into three groups(n=72): the control group(group A), the sham anesthesia group(group B), and the anesthesia group(group C). The anesthesia management was a 4-hour exposure to the 0.8 MAC (2.11%) sevoflurane. The expression of the PARP-1 and GABAAR α1/α2 in the hippocampus was examined by western blotting at 6, 24, 72 h after anesthesia, respectively. Open-field test were then performed separately when the rats were 5, 8, 14?蛳week?蛳old, respectively. Results Compared with group A(100%), the expression of the PARA?蛳1 was significantly increased at 6 h after sevoflurane exposure in group C [(216±15)%, P<0.05], and the ratio of α1/α2 subgroup of GABAAR was significantly increased at 6 h [(126±6)%], 24 h [(127±8)%], and 72 h [(183±22)%] after sevoflurane exposure (P<0.05). Both the expression of PARP-1 and the ratio of α1/α2 subgroup of GABAAR was of no significant difference between group A and group B. Rats exposed to sevoflurane(group C) showed a longer travel distance and time than that in group A underwent open-field test when they were 5 weeks old(P<0.05), and there was no significant difference in the activities between group A and group B(P>0.05). While no differences were seen in the activities when rats were 8 and 14 weeks old(P>0.05). Conclusions The exposure of sevoflurane can induce the apoptosis of neurons at early stage, indicated by the α1/α2 subgroup of GABAAR increasing. Sevoflurane might affect the adaptation and cognition ability of environment in the short term in neonatal rats.

Key words: Sevoflurane; Neonatal rats; Poly(ADP-ribose) polymerase-1; γ-aminobutyric acid subtype A receptor; Cognitive ability