Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.
Guizhou Key Laboratory of Basic Research of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.
Pediatr Res. 2023 Mar;93(4):838-844. doi: 10.1038/s41390-022-01943-x. Epub 2022 Jul 8.
The aim of the study was to determine the effects of repeated anesthesia exposure across postnatal development.
Seventy-two newborn Sprague-Dawley rats were randomly divided into Sev group and Con-aged group. Sev groups were exposed to 2.6% sevoflurane for 2 h on postnatal day (P) 7, P14, and P21; the Con groups only received carrier gas for 2 h. Learning and memory were evaluated using the MWM test at P31 (juvenile), P91 (adult), and 18 months postnatally (aged). The relative expression of APP and Mapt mRNA was detected by RT-PCR, while Aβ, tau, and P-tau protein levels were analyzed by immunohistochemistry.
After repeated inhalation of sevoflurane, MWM test performance was significantly decreased in the Sev-aged group compared to the Con-aged group (P > 0.05). The relative expression of APP and Mapt mRNA was not significantly different between groups in each growth period (P > 0.05). The tau expression in the juvenile hippocampal CA1, CA3, and dentate gyrus regions increased markedly in the Sev group, while P-tau only increased in the hippocampal CA3 region in the Sev-adult group. The expression of tau, P-tau, and Aβ in the hippocampal regions was upregulated in the Sev-aged group.
Multiple exposures to sevoflurane across postnatal development can induce or aggravate cognitive impairment in old age.
Whether multiple sevoflurane exposures across postnatal development cause cognitive impairment in childhood, adulthood, or old age, as well as the relationship between sevoflurane and the hippocampal Aβ, tau, and P-tau proteins, remains unknown. This study's results demonstrate that multiple exposures to sevoflurane across postnatal development do not appear to affect cognitive function in childhood and adulthood; however, multiple exposures may lead to a cognitive function deficit in old age. The underlying mechanism may involve overexpression of the tau, P-tau, and Aβ proteins in the hippocampus.
本研究旨在确定在出生后发育过程中反复麻醉暴露的影响。
72 只新生 Sprague-Dawley 大鼠随机分为 Sev 组和 Con-aged 组。Sev 组在出生后第 7、14 和 21 天每天暴露于 2.6%七氟醚 2 小时；Con 组仅接受载体气体 2 小时。在 P31（幼年期）、P91（成年期）和出生后 18 个月（老年期）使用 MWM 测试评估学习和记忆能力。通过 RT-PCR 检测 APP 和 Mapt mRNA 的相对表达，通过免疫组织化学分析 Aβ、tau 和 P-tau 蛋白水平。
重复吸入七氟醚后，Sev-aged 组在 MWM 测试中的表现明显低于 Con-aged 组（P > 0.05）。在每个生长阶段，APP 和 Mapt mRNA 的相对表达在各组之间均无显著差异（P > 0.05）。在幼年期，Sev 组海马 CA1、CA3 和齿状回区的 tau 表达明显增加，而 Sev 成年组仅在海马 CA3 区增加 P-tau。在 Sev-aged 组，海马区的 tau、P-tau 和 Aβ表达上调。
在出生后发育过程中多次接触七氟醚可导致老年时认知功能障碍加重或恶化。
多次接触七氟醚在出生后发育过程中是否会导致儿童期、成年期或老年期的认知障碍，以及七氟醚与海马 Aβ、tau 和 P-tau 蛋白之间的关系，目前尚不清楚。本研究结果表明，多次暴露于七氟醚在出生后发育过程中似乎不会影响儿童和成年期的认知功能；然而，多次暴露可能导致老年时认知功能缺陷。其潜在机制可能涉及海马 tau、P-tau 和 Aβ蛋白的过度表达。
