Wang Yiyao, Li Yu, Xing Qunzhi, Han Xuechan G, Dong Xu, Lu Yiping, Zhou Mintao
Department of Anesthesiology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
Mol Med Rep. 2017 May;15(5):2753-2759. doi: 10.3892/mmr.2017.6316. Epub 2017 Mar 13.
Due to the rapid development of medical technology used to perform intrauterine procedures during pregnancy, the number of patients receiving fetal surgery under general anesthesia is increasing. The aim of the present study was to determine the effects of anesthetics on the offspring of rats, and to identify the potential mechanisms underlying these effects. On day 14 of pregnancy, Sprague‑Dawley rats were equally divided into the following 3 groups (n=9): Control group (n=3), 3% sevoflurane group (n=3) and 4% sevoflurane group (n=3). Following birth of the offspring, the juvenile rats were assessed using an open‑field test, Morris water maze and a continuous passive avoidance test on different days to determine their learning abilities and memory. Western blot and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses were used to examine the expression of multiple critical factors associated with the proliferation and apoptosis of nerve cells, including Ki67, nestin, B cell leukemia/lymphoma 2 (Bcl-2), BCL2 associated X (Bax) and caspase‑3. Additionally, the level of adenosine triphosphate production among the 3 groups were compared. Furthermore, expression alterations in of glycogen synthase kinase‑3β (GSK‑3β) and β‑catenin were examined. The Morris water maze experiment revealed that an increased concentration of sevoflurane exposure significantly reduced the learning and memory abilities of the juvenile rats when compared with controls. In addition, western blotting and RT-qPCR analyses determined that the protein and mRNA expression levels of Bax, caspase‑3 and GSK‑3β were significantly increased relative to the controls. By contrast, the expression levels of nestin, Ki‑67, Bcl‑2 and β‑catenin were significantly reduced. The results of the present study suggest that exposure of pregnant mice to sevoflurane anesthesia demonstrates a negative effect on the learning and memory abilities of their offspring, and the Wnt/β-catenin signaling pathway may be involved in this process.
由于用于孕期宫内手术的医学技术迅速发展，接受全身麻醉下胎儿手术的患者数量正在增加。本研究的目的是确定麻醉剂对大鼠后代的影响，并确定这些影响背后的潜在机制。在妊娠第14天，将斯普拉格-道利大鼠平均分为以下3组（n = 9）：对照组（n = 3）、3%七氟醚组（n = 3）和4%七氟醚组（n = 3）。后代出生后，在不同天数使用旷场试验、莫里斯水迷宫和连续被动回避试验对幼鼠进行评估，以确定它们的学习能力和记忆力。采用蛋白质免疫印迹法和逆转录-定量聚合酶链反应（RT-qPCR）分析来检测与神经细胞增殖和凋亡相关的多个关键因子的表达，包括Ki67、巢蛋白、B细胞淋巴瘤/白血病-2（Bcl-2）、BCL2相关X蛋白（Bax）和半胱天冬酶-3。此外，比较了3组之间三磷酸腺苷的产生水平。此外，还检测了糖原合酶激酶-3β（GSK-3β）和β-连环蛋白的表达变化。莫里斯水迷宫实验表明，与对照组相比，七氟醚暴露浓度增加显著降低了幼鼠的学习和记忆能力。此外，蛋白质免疫印迹法和RT-qPCR分析确定，与对照组相比，Bax、半胱天冬酶-3和GSK-3β的蛋白质和mRNA表达水平显著升高。相比之下，巢蛋白、Ki-67、Bcl-2和β-连环蛋白的表达水平显著降低。本研究结果表明，怀孕小鼠暴露于七氟醚麻醉对其后代的学习和记忆能力有负面影响，且Wnt/β-连环蛋白信号通路可能参与了这一过程。
