Numerous studies have shown that the inhaled general anesthetic sevoflurane imposes toxicity on the central nervous system during the developmental period but the underlying mechanisms remain unclear. Neuropeptide Y (NPY) was reported to have important neuroprotective effects, which can attenuate neuronal loss under pathological conditions. However, the effects of NPY on sevoflurane-induced hippocampal neuronal apoptosis have not been investigated. In this study, postnatal day 7 (PND7) Sprague-Dawley rats and primary cultured cells separated from hippocampi were exposed to sevoflurane (2.4% for 4 h) and the NPY expression levels after treatment were analyzed. Furthermore, neuronal apoptosis assay was conducted via immunofluorescence staining of cleaved caspase-3 and flow cytometry after exogenous NPY administration to PND7 rats as well as cultured hippocampal neurons to elucidate the role of NPY in sevoflurane-induced neurotoxicity. Our results showed the level of NPY gradually decreased within 24 h after sevoflurane exposure in both the hippocampus of PND7 rats and cultured hippocampal neurons, but not in cultured astrocytes. In the exogenous NPY pretreatment study, the proportion of cleaved caspase-3 positive cells in the CA1 region of the hippocampus was increased significantly at 24 h after sevoflurane treatment, while NPY pretreatment could reduce it. Similarly, NPY could also reverse the apoptogenic effect of sevoflurane on cultured neurons. Herein, our results showed that sevoflurane caused a significant decrease in NPY expression, whereas exogenous NPY supplementation could reduce sevoflurane-induced hippocampal neuronal apoptosis both in vivo and in vitro.

中文翻译：

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七氟醚通过改变新生大鼠中神经肽Y的水平诱导海马神经元凋亡。

大量研究表明，吸入的全身麻醉药七氟醚在发育期间会对中枢神经系统产生毒性，但其潜在机制尚不清楚。据报道，神经肽Y（NPY）具有重要的神经保护作用，可以减轻病理条件下的神经元丢失。然而，尚未研究NPY对七氟醚诱导的海马神经元凋亡的影响。在这项研究中，将出生后第7天（PND7）的Sprague-Dawley大鼠和从海马体分离的原代培养细胞暴露于七氟醚中（2.4％持续4 h），并分析治疗后的NPY表达水平。此外，在对PND7大鼠和培养的海马神经元外源性NPY给药后，通过裂解caspase-3的免疫荧光染色和流式细胞术进行神经元凋亡测定，以阐明NPY在七氟醚引起的神经毒性中的作用。我们的研究结果显示，在七氟醚暴露后24小时内，PND7大鼠和培养的海马神经元中的NPY水平逐渐降低，但在培养的星形胶质细胞中却没有。在外源性NPY预处理研究中，七氟醚处理后24 h，海马CA1区裂解的caspase-3阳性细胞的比例显着增加，而NPY预处理则可以减少。同样，NPY也可以逆转七氟醚对培养的神经元的凋亡作用。在这里