重复异丙酚麻醉对新生大鼠海马细胞凋亡及远期学习记忆能力的影响

doi:10.3969/j.issn.1671-167X.2017.02.022

北京大学学报(医学版) ›› 2017, Vol. 49 ›› Issue (2): 310-314. doi: 10.3969/j.issn.1671-167X.2017.02.022

重复异丙酚麻醉对新生大鼠海马细胞凋亡及远期学习记忆能力的影响

王玉洁，郭向阳，王军△

（北京大学第三医院麻醉科，北京100191）

出版日期:2017-04-18 发布日期:2017-04-18
通讯作者: 王军 E-mail:luckyoldhorse@sina.com
基金资助:
国家自然科学基金（21342016）资助

Influences of repeated propofol anesthesia on hippocampal apoptosis and long-term learning and memory abilities of neonatal rats

WANG Yu-jie, GUO Xiang-yang, WANG Jun△

(Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China)

Online:2017-04-18 Published:2017-04-18
Contact: WANG Jun E-mail:luckyoldhorse@sina.com
Supported by:
Supported by the National Natural Science Foundation of China (21342016)

摘要/Abstract

摘要：

目的：探讨重复异丙酚麻醉对新生大鼠海马细胞凋亡及远期学习记忆能力的影响。方法：清洁级SD大鼠45只，7 d龄，雄性，随机分为3组（n=15）：对照组（C组）腹腔注射脂肪乳剂7.5 mL/kg，每天1次，连续7 d；反复注射异丙酚组（P1组）腹腔注射异丙酚75 mg/kg，每天1次，连续7 d；单次注射异丙酚组（P2组）腹腔注射脂肪乳剂7.5 mL/kg，每天1次，连续6 d，第7天注射异丙酚75 mg/kg。每组取5只大鼠，于苏醒后即刻抽取动脉血样行血气分析。异丙酚给药结束后2周时采用Morris水迷宫实验测试大鼠的学习记忆功能，之后处死大鼠，免疫组织化学法检测大鼠海马神经元特异性核蛋白（neuron-specific nucleoprotein，NeuN）的表达，Western blot检测大鼠海马组织中caspase-3的表达。结果： 3组大鼠动脉血气指标差异无统计学意义。与C组相比，P1组大鼠第5天寻找平台潜伏期延长、寻找平台路径增长，第6天目标象限探索时间缩短、穿环次数减少（P<0.05）；而P2组的寻找平台潜伏期、寻找平台路径长度、探索时间、穿环次数与C组相比差异无统计学意义。与C组相比，P1组大鼠海马组织内NeuN阳性细胞数量减少、caspase3表达增强；P2组大鼠海马内NeuN阳性细胞数量、caspase-3的表达与C组相比差异无统计学意义。结论：重复异丙酚麻醉可降低新生大鼠的远期学习记忆能力，可能与其增加海马内的细胞凋亡有关，单次异丙酚麻醉对新生大鼠的海马细胞凋亡及远期学习记忆能力没有显著影响。

关键词: 二异丙酚, 细胞凋亡, 认知障碍, 大鼠, Sprague-Dawley

Abstract:

Objective： To investigate the influences of repeated propofol anesthesia on the hippocampal apoptosis and the long-term learning and memory abilities of neonatal rats. Methods: In the study, 45 male Sprague-Dawley rats, aged 7 days, were randomly divided into 3 group (n=15 each): control group (C group) that received intralipid 7.5 mL/kg intraperitioneal (IP) once a day×7 days; group propofol 1 (P1) that received propofol 75 mg/kg IP once a day×7 days; group propofol 2 (P2) that received intralipid 7.5 mL/kg IP once a day×6 days+propofol 75 mg/kg IP on the 7th day. In each group, 5 animals were chosen and arterial blood samples were obtained immediately after the animals were fully awake for blood gas analysis. Learning and memory abilities were assessed using Morris water maze when the other rats were 4 weeks old. The animals were decapitated after the tests. The hippocampi were isolated for detection of neuron-specific nucleoprotein (NeuN) expression by immunohistochemistry method and the expression of caspase-3 using the Western blot. Results: There was no significant difference in the indexes of blood gas analysis among the 3 groups. Morris water maze test: compared with group C, the escape latency and the length of searching on the 5th day were significantly prolonged, and the searching time in target quadrant and platform crossing on the 6th day were significantly decreased in group P1 (P<0.05) but not in group P2. Compared with group C, NeuN-positive neurons were decreased, and the expression of caspase-3 was increased in the rats of group P1 (P<0.05) but not in group P2. Conclusion: Repeated propofol anesthesia may destroy longterm learning and memory abilities by inducing apoptosis of hippocampal neurons in neonatal rats, while single dose of propofol has no obvious effect on the hippocampal apoptosis and longterm learning and memory of neonatal rats.

Key words: Propofol, Apoptosis, Cognition disorders, Rats, Sprague-Dawley

中图分类号:

R338

王玉洁，郭向阳，王军. 重复异丙酚麻醉对新生大鼠海马细胞凋亡及远期学习记忆能力的影响[J]. 北京大学学报(医学版), 2017, 49(2): 310-314.

WANG Yu-jie, GUO Xiang-yang, WANG Jun. Influences of repeated propofol anesthesia on hippocampal apoptosis and long-term learning and memory abilities of neonatal rats[J]. Journal of Peking University(Health Sciences), 2017, 49(2): 310-314.

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重复异丙酚麻醉对新生大鼠海马细胞凋亡及远期学习记忆能力的影响

Influences of repeated propofol anesthesia on hippocampal apoptosis and long-term learning and memory abilities of neonatal rats

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