七氟烷、异氟烷对幼鼠脑细胞凋亡和远期学习记忆功能的影响

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (5): 495-500.

七氟烷、异氟烷对幼鼠脑细胞凋亡和远期学习记忆功能的影响

斯小龙¹, 李国政², 刘小南¹, 徐宏明¹, 彭从斌²

¹临安市人民医院麻醉科,临安311300,浙江;
²浙江省立同德医院麻醉科,杭州310012,浙江

收稿日期:2013-03-02 修回日期:2013-05-09 出版日期:2013-05-26 发布日期:2013-05-22
通讯作者: 彭从斌,男,本科,主任医师,研究方向:围术期脏器保护。Tel: 18868723530 E-mail: jhydlgz@163.com
作者简介:斯小龙,男,硕士,副主任医师,研究方向:小儿麻醉。Tel: 13868023368 E-mail: jhlgz@tom.com
基金资助:
国家自然科学基金(81271204);浙江省自然科学基金(Y205219)

Effects of sevoflurane and isoflurane on neuroapoptosis and the long-term learning ability in newborn rat brain

SI Xiao-long¹, LI Guo-zheng², LIU Xiao-nan¹, XU Hong-ming¹, PENG Cong-bin²

¹Department of Anesthesiology,Linan People's Hospital,Linan 311300,Zhejiang, China;
²Department of Anesthesiology,Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang ,China

Received:2013-03-02 Revised:2013-05-09 Online:2013-05-26 Published:2013-05-22

摘要/Abstract

摘要： 目的: 观察幼鼠暴露于七氟烷、异氟烷不同时间对脑细胞凋亡及远期学习记忆能力的影响。方法: 出生后 7 d Wistar幼鼠90只随机分为5组:模拟麻醉(A组),3.6%七氟烷麻醉 2 h(B组),3.6%七氟烷麻醉 6 h(C组),2.3%异氟烷麻醉 2 h(D组),2.3%异氟烷麻醉 6 h(E组),每组幼鼠麻醉中均无缺氧及CO₂蓄积发生。麻醉结束 6 h 后采用4%多聚甲醛灌注取脑,免疫组化检测caspase-3蛋白表达;余幼鼠分别在成长至5、14周时,行Morris水迷宫实验后检测脑caspase-3蛋白表达(n=6)。结果: 与A组相比,B、C、D及E组海马齿状回及CA3区caspase-3阳性细胞数明显增加,且C组多于B组,E组多于D组(P<0.05)。各组大鼠5、14周定位航行实验每日到达平台所需游泳距离无统计学差异,游泳速度、第一次穿越原平台位置时间、原平台所在象限游泳时间无统计学差异(P>0.05),但B、C、D及E组大鼠穿越原平台所在位置次数明显高于A组(P<0.05)。结论: 发育期幼鼠暴露于 3.6%七氟烷和 2.3%异氟烷均能诱发海马神经元细胞凋亡,等效浓度异氟烷影响超过七氟烷;两药均一过性影响大鼠对不良刺激的记忆能力,但未造成大鼠远期空间记忆能力下降。

关键词: 七氟烷, 异氟烷, 幼鼠, caspase-3, 空间记忆

Abstract: AIM: To investigate the changes of neuroapoptosis in brain and learning ability after neonatal mice exposed to inhaled sevoflurane or isoflurane.METHODS: Ninety postnatal day(P)7 Wistar rats were randomly divided into 5 groups : group A sham anesthesia,group B 3.6% sevoflurane for 2 h, group C 3.6% sevoflurane for 6 h, group D 2.3% isoflurane for 2 h and group E 2.3% isoflurane for 6 h. Animals from each group were perfused transcardially with 0.1 mol phosphate buffer containing 4% paraformaldehyde 6 h after the end of anesthesia, and then the brains were exposed for immunohisochemistry, caspase-3 positive cells were detected. Behavioral studies with Morris water maze test were performed separately when the rats were 5-week-old and 14-week-old.RESULTS: The amounts of caspase-3 positive cells in the rats brain of Group B, C,D and E were greater than that in Group A, and the amount in group C was greater than that in gourp B, in group E more than that in group B(P<0.05). When face the spatial reference memory task or space exploration task, rats from different groups make it uniformly. Anesthetic rats and control rats performed similarly in terms of path length when learning to swim to the platform during locating trials. No rats showed significantly higher levels of retention during the probe trials in terms of target quadrant time, platform crossings and platform location time(P>0.05),but the number of platform crossings in group B,C,D and E was significantly higher than that in gourp A(P<0.05).CONCLUSION: Exposure to the concentration of 3.6% sevoflurane or 2.3% isoflurane could cause brain cell apoptosis of newborn rats. Isoflurane could cause more insults to brain than sevoflurane at an equivalent concentration. The memory ability to pessimal stimulation is decreased as the anesthesia mice 5 weeks old, such changes recede along with the growth of rats. Exposure to sevoflurane and isoflurane does not affect the spatial reference memory of newborn rat during their growth.

Key words: Sevoflurane, Isoflurane, Newborn rats, caspase-3, Spatial reference memory

中图分类号:

R965.2

斯小龙, 李国政, 刘小南, 徐宏明, 彭从斌. 七氟烷、异氟烷对幼鼠脑细胞凋亡和远期学习记忆功能的影响[J]. 中国临床药理学与治疗学, 2013, 18(5): 495-500.

SI Xiao-long, LI Guo-zheng, LIU Xiao-nan, XU Hong-ming, PENG Cong-bin. Effects of sevoflurane and isoflurane on neuroapoptosis and the long-term learning ability in newborn rat brain[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(5): 495-500.

参考文献

[1] Loepke AW, Soriano SG. An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function[J]. Anesth Analg, 2008, 106(6): 1681-1707.
[2] Anand KJ, Soriano SG. Anesthetic agents and the immature brain: are these toxic or therapeutic[J] ? Anesthesiology, 2004, 101(2): 527-530.
[3] Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits[J]. J Neurosci, 2003, 23(3): 876-882.
[4] Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children[J]. Anesth Analg, 2007, 104(3): 509-520.
[5] Satomoto M, Satoh Y, Terui K, et al. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice[J]. Anesthesiology, 2009, 110(3): 628-637.
[6] Fredriksson A, Ponten E, Gordh T, et al. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits[J]. Anesthesiology, 2007, 107(3): 427-436.
[7] Tu S, Wang X, Yang F, et al. Propofol induces neuronal apoptosis in infant rat brain under hypoxic conditions[J]. Brain Res Bull, 2011, 86(1/2): 29-35.
[8] Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain[J]. Science, 1999, 283(5398): 70-74.
[9] Stratmann G, Sall JW, May LD, et al. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats[J]. Anesthesiology, 2009, 110(4): 834-848.
[10] Piehl E, Foley L, Barron M, et al. The effect of sevoflurane on neuronal degeneration and GABA_A subunit composition in a developing rat model of organotypic hippocampal slice cultures[J]. J Neurosurg Anesthesiol, 2010, 22(3): 220-229.
[11] Peng S, Zhang Y, Sun DP, et al. The effect of sevoflurane anesthesia on cognitive function and the expression of Insulin-like Growth Factor-1 in CA1 region of hippocampus in old rats[J]. Mol Biol Rep, 2011, 38(2): 1195-1199.
[12] Shih J, May LD, Gonzalez HE, et al. Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats[J]. Anesthesiology, 2012, 116(3): 586-602.
[13] 胡镜清, 温泽淮, 赖世隆. Morris水迷宫检测的记忆属性与方法学初探[J]. 广州中医药大学学报, 2000, 17(2): 117-119.

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