北京大学学报(医学版) ›› 2015, Vol. 47 ›› Issue (4): 674-678. doi: 10.3969/j.issn.1671-167X.2015.04.025

• 论著 • 上一篇    下一篇

七氟烷对幼鼠脑细胞凋亡和远期学习记忆功能的影响

郑少强1,陈雪1,王雅杰2,安立新3△   

  1. (1.北京积水潭医院麻醉科,北京100035;2.首都医科大学附属北京天坛医院临床中心实验室,北京100050;3. 首都医科大学附属北京天坛医院麻醉科,北京100050)
  • 出版日期:2015-08-18 发布日期:2015-08-18
  • 通讯作者: 安立新 E-mail:anlixin8120@163.com
  • 基金资助:

    首都医科大学基础-临床合作基金(JL-1047)资助

Effects of sevoflurane on brain neuroapoptosis and ability of long-term learning and memory  in newborn rats

ZHENG Shao-qiang1, CHEN Xue1, WANG Ya-jie2, AN Li-xin3△   

  1. (1.Department of Anesthesiology, Beijing Jishuitan Hospital, Beijing 100035, China; 2. Department of Clinical Laboratory, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; 3. Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China)
  • Online:2015-08-18 Published:2015-08-18
  • Contact: AN Li-xin E-mail:anlixin8120@163.com
  • Supported by:

    Supported by Capital Medical University Basic Clinical Cooperation Fund (JL-1047)

摘要:

目的:观察幼鼠暴露于不同浓度七氟烷不同时间后,脑细胞凋亡及远期学习记忆、空间探索能力的变化,探讨脑细胞凋亡与认知功能障碍的关系。方法:出生后7 d的Wistar幼鼠21只随机分为7组行预实验,选出无二氧化碳蓄积的麻醉方案。出生后7 d的Wistar幼鼠90只随机分为5组:模拟麻醉(A组)、1%(体积分数)七氟烷麻醉2 h(B组)和4 h(C组)、2%(体积分数)七氟烷麻醉2 h(D组)和4 h(E组),麻醉结束6 h后,每组6只幼鼠,多聚甲醛灌注取脑,免疫组织化学方法检测半胱氨酸天冬氨酸蛋白酶3(caspase-3)表达。其余幼鼠分别在成长至5、8、14周时,进行Morris水迷宫实验和避暗实验。结果:与A组相比,B、D及E组在海马齿状回及CA3区等脑区caspase-3阳性细胞数明显增加(P<0.05)。各组幼鼠各阶段Morris水迷宫观察指标差异无统计学意义(P>0.05),七氟烷麻醉组在5周时避暗反应差于模拟麻醉组,第8周时与模拟麻醉组无差别。结论:发育期幼鼠暴露于2%七氟烷可诱发海马神经元凋亡,同时一过性影响幼鼠对不良刺激的记忆能力;暴露于2%七氟烷不会造成幼鼠空间记忆能力下降。

关键词: 七氟烷, 细胞凋亡, 认知障碍, 半胱氨酸天冬氨酸蛋白酶3, 大鼠, Wistar

Abstract:

Objective: To investigate the changes of neuroapoptosis in brain and learning ability after neonatal mice are exposed to inhaled sevoflurane.Methods: Twenty-one postnatal day (P) 7 Wistar rats were randomly divided into 7 groups for the preliminary experiment. Arterial blood samples were obtained immediately at the end of anesthesia, then blood analysis was performed. According to the results of the blood analysis, the groups that had no carbon dioxide accumulation were chosen for the following experiment. Ninety postnatal day (P) 7 Wistar rats were randomly divided into 5 groups: group A [sham anesthesia], group B [1% (volume fraction) sevoflurane for 2 h], group C (1% sevoflurane for 4 h), group D [2% (volume fraction) sevoflurane for 2 h] and group E (2% sevoflurane for 4 h). The animals from each group were perfused transcardially with 0.1 mol/L phosphate buffer containing 4% (volume fraction) paraformaldehyde 6 h after the end of anesthesia, and then the brains were exposed for immunohisochemistry, and caspase-3 positive cells were detected. Behavioral studies which included Morris water maze and passive voidance test were performed separately when the rats were 5-week-old, 8-week-old and 14-week-old. Results: The blood gas data in the mice during the anesthesia showed that the pH, arterial carbon dioxide tension, arterial oxygen tension, and arterial oxygen saturation did not differ significantly from those of the sham controls. The amount of the caspase-3 positive cells in the rat brains of group B, group D and group E was greater than that in group A. When facing the spatial reference memory task or space exploration task, the rats from the different groups made it uniformly. The rats exposed to sham anesthesia had longer latency and less mistake times than those to sevoflurane in passive voidance test when they were 5-week-old, while all the rats had no significant difference in 8 weeks. Conclusion: Exposure to the concentration of 2% sevoflurane causes brain cell apoptosis of newborn rats. The memory ability to pessimal stimulation is decreased as the anesthesia mice were 5-week-old, such changes recede along with the growth of the rats. Exposure to the concentration of 2% sevoflurane does not affect the spatial reference memory of newborn rats during their growth.

Key words: Sevoflurane, Apoptosis, Cognition disorders, Caspase-3, Rats, Wistar

中图分类号: 

  • R614.1
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