Sevoflurane Induces Hippocampal Neuronal Apoptosis by Altering the Level of Neuropeptide Y in Neonatal Rats
Sevoflurane Induces Hippocampal Neuronal Apoptosis by Altering the Level of Neuropeptide Y in Neonatal Rats
复制标题
七氟醚通过改变新生大鼠神经肽 Y 的水平诱导海马神经元凋亡
DOI：
10.1007/s11064-020-03028-9
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发表时间：
2020-05-06
影响因子：
4.4
通讯作者：
Feng, Xia
中科院分区：
文献类型：
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作者：
Kang, Wenbin;Lu, Dihan;Feng, Xia
大量研究表明，吸入全身麻醉剂七氟烷在发育期对中枢神经系统产生毒性，但其潜在机制尚不清楚。神经肽Y（neuropeptide Y，NPY）具有重要的神经保护作用，可减轻病理状态下神经元的损伤。然而，神经肽Y对七氟醚诱导的海马神经元凋亡的影响还没有研究。在本研究中，出生后第7天（PND 7）的Sprague-Dawley大鼠和从大鼠中分离的原代培养细胞暴露于七氟烷（2.4%，持续4 h），并分析处理后的NPY表达水平。此外，通过免疫荧光染色和流式细胞术对外源性NPY给药后PND 7大鼠以及培养的海马神经元进行神经细胞凋亡测定，以阐明NPY在七氟醚诱导的神经毒性中的作用。结果显示，七氟醚暴露后24 h内，PND 7大鼠海马和培养的海马神经元中NPY水平均逐渐下降，而培养的星形胶质细胞中NPY水平无明显变化。在外源性NPY预处理研究中，七氟醚处理后24 h海马CA 1区caspase-3阳性细胞比例显著增加，而NPY预处理可使其减少，同样，NPY也可逆转七氟醚对培养神经元的致凋亡作用。在此，我们的研究结果表明，七氟醚引起的NPY表达显着下降，而外源性NPY补充可以减少七氟醚诱导的海马神经元凋亡在体内和体外。
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.