七氟醚可引起新生小鼠发育期大脑记忆功能损伤
祝贺贵州医科大学麻醉学院15级科学学位研究生郭唯真顺利毕业
研究方向：机械通气肺损伤 指导老师：高鸿教授 高巨教授
研究生期间共发表文章3篇，其中北图核心2篇，参与国家自然科学基金项目1项
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Sevoflurane-induced memory impairment in the postnatal developing mouse brain
背景与目的
本研究旨在证实七氟醚能引起新生小鼠发育期记忆功能损伤，并探讨其作用机制。
方 法
将7日龄的C57BL/6小鼠随机分配到2.6%七氟醚组（n=68）、1.3%七氟醚组(n=68)和对照组（n=38）。利用血气分析来评估麻醉过程中78只小鼠的缺氧和呼吸抑制情况，用免疫组化对半胱天冬酶-3(caspase-3)的表达进行检测，使用蛋白免疫印迹法(western blotting)对聚腺苷二磷酸核酸转移酶(PARP)的裂解情况进行分析。此外，为了检测来自各试验组12只小鼠的海马脑源性神经营养因子(BDNF)、酪氨酸激酶受体-2(Ntrk2)、前-脑源性神经营养因子(pro-BDNF)、p75神经营养因子受体(p75NTR)和蛋白激酶B（PKB/Akt）的含量，使用酶联免疫吸附试验(enzyme-linked immunosorbent assay)进行测定。并运用莫里斯水迷宫(MWM)实验对60只小鼠进行行为学测试。
结 果
MWM测试结果显示,吸入2.6%和1.3%七氟醚组的小鼠在平台象限中的逗留时间明显低于对照组，其caspase-3含量和PARP的裂解显著高于对照组。此外，持续吸入2.6%七氟醚的试验组小鼠pro-BDN和p75NTR含量明显升高，而PKB/Akt含量显著降低。最终，MWM测试结果表明，七氟醚能使新生小鼠的记忆功能受损。
结 论
目前研究结果提示caspase-3诱导的PARP分裂，pro-BDNF、p75NTR和PKB/Akt含量的变化在七氟醚诱导--引起新生小鼠大脑的记忆功能损伤机制中可能发挥着至关重要的作用。
原始文献摘要
ZHIJUN LU, JIHUI SUN, YICHUN XIN；Sevoflurane-induced memory impairment in the postnatal developing mouse brain；EXPERIMENTAL AND THERAPEUTIC MEDICINE 15: 4097-4104, 2018
Objective
The aim of the present study was to confirm that sevoflurane induces memory impairment in the postnatal developing mouse brain and determine its mechanism of action.
Methods
C57BL/6 mice 7 days old were randomly assigned into a 2.6% sevoflurane (n=68), a 1.3% sevoflurane (n=68) and a control (n=38) group. Blood gas analysis was performed to evaluate hypoxia and respiratory depression during anes-thesia in 78 mice. Measurements for expression of caspase‑3 by immunohistochemistry, cleavage of poly adenosine diphosphate‑ribose polymerase (PARP) by western blotting, as well as levels of brain‑derived neurotrophic factor (BDNF), tyrosine kinase receptor type 2 (Ntrk2), pro‑BDNF, p75 neuro-trophin receptor (p75NTR) and protein kinase B (PKB/Akt) by enzyme-linked immunosorbent assay were performed in the hippocampus of 12 mice from each group. A total of 60 mice underwent the Morris water maze (MWM) test.
Results
Results from the MWM test indicated that the time spent in the northwest quadrant and platform site crossovers by mice in the 2.6 and 1.3% sevoflurane groups was significantly lower than that of the control group. Meanwhile, levels of caspase‑3 and cleaved PARP in the 2.6 and 1.3% sevoflurane groups were significantly higher than that in the control group. Levels of pro‑BDNF and p75NTR were significantly increased and the level of PKB/Akt was significantly decreased following exposure to 2.6% sevoflurane. Finally, the memory of post-natal mice was impaired by sevoflurane, this was determined using a MWM test.
Conclusions
the results of the current study suggest that caspase‑3 induced cleavage of PARP, as well as pro‑BDNF, p75NTR and PKB/Akt may be important in sevoflurane-induced memory impairment in the postnatal developing mouse brain.
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