低温对丙泊酚麻醉下新生大鼠学习记忆能力和海马细胞凋亡的影响

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Effects of hypothermia during propofol anesthesia on

learning and memory ability and hippocampal apoptosis in neonatal rats

背景与目的

目前,低温对中枢神经系统的危害已引起学者的高度重视。本研究的目的是探讨

低温对新生大鼠学习记忆能力和海马细胞凋亡的影响以及p-ERK和p-CREB在麻醉中的作用。

方  法

本研究将60只SD新生大鼠(7日龄)随机分为3组(n = 20),包括对照组(C

组)、麻醉组(A组)和低温麻醉组(AH组)。C组腹腔注射0.1ml生理盐水,且直肠温度保持在38-39℃; A组腹腔注射25mg/kg丙泊酚(0.1ml),且每间隔20分钟追加1/2初始剂量,麻醉维持时间为2小时,直肠温度保持在38-39℃。AH组的麻醉方式和麻醉持续时间与A组相同,将室温设定为23℃,从而使体温自然下降。麻醉恢复后,各组随机抽取5只大鼠进行Western blot分析,检测p-ERK和p-CREB的表达水平,通过流式细胞仪检测其他5例大鼠的海马细胞凋亡率。将每组剩余10只大鼠喂养至30天并进行Morris水迷宫试验,检测各组5只大鼠p-ERK和p-CREB的表达水平,以及海马细胞凋亡率。

结  果

与C组和A组相比,AH组直肠温度明显降低(P <0.05); 在第7天时,与C组和A组相比,AH组海马细胞凋亡率增加(P <0.05),AH组p-ERK和p-CREB蛋白表达水平显著降低( P <0.05),C组与A组之间差异无统计学意义。在第36天时,行为测试结果、海马细胞凋亡率和蛋白表达的水平无显著差异。

结  论

我们的研究结果表明,麻醉中低温可以增加新生大鼠海马细胞的凋亡率,其机制

可能与p-ERK和p-CREB的下调有关。但其对长期的学习和记忆能力没有明显的影响。

                                                原始文献摘要

Liu W 1,  Tan X 2,  Xiong X 3,  Yang J 4,  Xiao X X 5.Effects of hypothermia during propofol anesthesia on learning and memory ability and hippocampal apoptosis in neonatal rats.  J Anesth.  2018 Nov 17. doi: 10.1007/s00540- 018-2576-7.

Abstract

Objective At present, the harm of hypothermia to the central nervous system has received a great attention from scholars. The

present study aimed to investigate the effects of hypothermia on learning and memory abilities and hippocampal apoptosis in neonatal rats and the role of p-ERK and p-CREB in anesthesia.

Methods In this study, 60 Sprague Dawley newborn rats (age 7-day-old) were randomly divided into 3 groups (n = 20), including Control Group (Group C), Anesthesia Group (Group A), and Anesthesia Hypothermia Group (Group AH). Group C was intraperitoneally injected with 0.1 ml saline, and rectal temperature was maintained in the range of 38–39 °C; Group A was intraperitoneally injected with 25 mg/kg of propofol (0.1 ml), the 1/2 initial dose was added per each period of 20 min, anesthesia was maintained for 2 h, and rectal temperature was kept in the range of 38–39 °C. The anesthesia mode and duration of Group AH were as same as Group A, room temperature was set to 23 °C, which caused body’s temperature naturally dropped down. After the anesthesia recovered, each group randomly involved five rats for analyzing by Western blot to detect the expression level of p-ERK and p-CREB, and other five rates were also analyzed by flow cytometry assay to detect hippocampal apoptosis rate. The remaining 10 rats in each group were kept up to 30 days for conducting the Morris water maze test, five rats were tested for detecting the expression level of p-ERK and p-CREB, as well as hippocampal apoptosis rate in each group.

Results Compared with Group C and Group A, the rectal temperature of Group AH was decreased significantly (P < 0.05);

At the age of 7 days, compared with Group C and Group A, apoptosis rate of hippocampal tissue in Group AH was increased

(P < 0.05), the expression level of p-ERK and p-CREB proteins in Group AH was significantly reduced (P < 0.05), and there were no significant differences between Group C and Group A. At the age of 36 days, there were no significant differences in the results of behavioral test, apoptotic rates, and expression level of the proteins.

Conclusion Our findings suggest that hypothermia during anesthesia can increase the apoptosis rate in the hippocampus of

neonatal rats, whose mechanism may be related to the downward adjustment of p-ERK and p-CREB. However, it has no obvious influence on the long-term learning and memory abilities.

罂粟花

麻醉学文献进展分享

                   贵州医科大学高鸿教授课题组

                     编辑:符校魁        审校:余晓旭

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