Department of Anesthesia, East Hospital of Shaoyang Central Hospital Medical Group, Shaoyang, 422000, China.
Department of Anesthesia, The Central Hospital of Shaoyang, Shaoyang, 422000, China.
J Anesth. 2019 Feb;33(1):9-16. doi: 10.1007/s00540-018-2576-7. Epub 2018 Nov 17.
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.
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.
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.
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.
目前，学者们对低温对中枢神经系统的危害给予了极大关注。本研究旨在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，以及麻醉中 p-ERK 和 p-CREB 的作用。
本研究将 60 只 7 日龄 Sprague Dawley 新生大鼠随机分为 3 组（n=20），包括对照组（C 组）、麻醉组（A 组）和麻醉低温组（AH 组）。C 组腹腔内注射 0.1ml 生理盐水，直肠温度维持在 38-39°C；A 组腹腔内注射 25mg/kg 丙泊酚（0.1ml），每 20min 加入 1/2初始剂量，麻醉持续 2h，直肠温度维持在 38-39°C。AH 组的麻醉方式和时间与 A 组相同，室温设定为 23°C，使体温自然下降。麻醉恢复后，每组随机抽取 5 只大鼠通过 Western blot 检测 p-ERK 和 p-CREB 的表达水平，另 5 只大鼠通过流式细胞术检测海马细胞凋亡率。每组剩余的 10 只大鼠持续至 30 天进行 Morris 水迷宫测试，5 只大鼠用于检测每组 p-ERK 和 p-CREB 的表达水平以及海马细胞凋亡率。
与 C 组和 A 组相比，AH 组直肠温度明显下降（P<0.05）；7 日龄时，与 C 组和 A 组相比，AH 组海马组织细胞凋亡率增加（P<0.05），p-ERK 和 p-CREB 蛋白表达水平明显降低（P<0.05），而 C 组和 A 组之间无明显差异。36 日龄时，行为测试结果、凋亡率和蛋白表达水平均无显著差异。
本研究结果表明，麻醉期间低温可增加新生大鼠海马细胞凋亡率，其机制可能与 p-ERK 和 p-CREB 下调有关，但对长期学习记忆能力无明显影响。
