Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blocker ZD7288 Prevents Sevoflurane-Induced Hyperactivity in a Novel Mice Behavioral Model

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blocker ZD7288 Prevents Sevoflurane-Induced Hyperactivity in a Novel Mice Behavioral Model
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超极化激活的环核苷酸门控通道阻滞剂 ZD7288 在新型小鼠行为模型中预防七氟烷诱导的多动症

DOI:
10.24015/japm.2017.0011
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发表时间:
2017-01
期刊:
J Anesth Perioper Med
影响因子:
--
通讯作者:
Cheng Zhou
Cheng Zhou
中科院分区:
其他
文献类型:
--
作者:
Peng Liang;XuBin Huang;Feng-Shan Li;Han Huang;JingXuan Qiu;Daqing Liao;Jin Liu;Cheng Zhou

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背景:除全身麻醉作用外,七氟醚在诱导和恢复过程中也会引起多动,特别是在幼儿中。缺乏令人满意的动物模型阻碍了对多动症病因的研究和预防。超极化激活环核苷酸门控(HCN)通道阻滞剂可能具有镇静作用。本研究建立了一种新的小鼠多动行为模型,并进一步探讨了HCN通道阻滞剂对七氟醚所致多动的影响。方法:以C57BL/6小鼠为实验对象。用行为跟踪软件定量测量小鼠的最大速度、平均速度、总运动距离和静息率。并对模型的年龄依赖性进行了分析。腹腔注射HCN通道阻滞剂ZD7288,剂量分别为6.25和12.5 μg/kg,以预防七氟醚所致的多动。结果:在行为模型中,吸入1%七氟醚后小鼠在恢复期出现明显的多动,表现为运动速度和总距离增加。七氟醚致幼鼠多动较成年鼠明显(P<0.01)。预给药ZD7288可显著预防七氟醚所致的多动症。结论:本研究建立的小鼠行为学模型在诱导期、恢复期、年龄依赖性等方面均能表征七氟醚致多动症。此外,通过该动物模型,HCN通道阻滞剂ZD7288可以预防七氟醚诱导的多动症。因此,HCN通道可能是全麻中七氟醚诱导躁动的潜在治疗靶点。引用本文:梁鹏,黄旭斌,李凤山,黄汉,邱景轩,廖大庆,等超极化激活的环核苷酸门控通道阻断剂ZD7288在一种新的小鼠行为模型中阻止七氟醚诱导的多动症。中华外科杂志2017;4: 205 - 12。doi: 10.24015/ japm .2017.0011这是一篇开放获取的文章,由Evidence Based Communications (EBC)发表。本作品遵循知识共享署名4.0国际许可协议,允许以任何媒介或格式出于任何合法目的不受限制地使用、分发和复制。要查看此许可证的副本,请访问http://creativecommons.org/licenses/by/4.0/。
Background: Besides effect of general anesthesia, sevoflurane also induces hyperactivity during induction and recovery, especially in young children. Lack of satisfied animal model impedes the investigation of causes of the hyperactivity as well as its prevention. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker might produce sedative effect. This study developed a novel mice model of hyperactive behaviors and further explored effects of HCN channel blocker on sevoflurane-induced hyperactivity.  Methods: C57BL/6 mice were used in the present study. Maximal speed, mean speed, total movement distance and resting percentage of mice were quantitatively measured by behavioral tracking software. Age-dependence of this model was also analyzed. HCN channel blocker ZD7288 at doses of 6.25 and 12.5 μg/kg were intraperitoneal injected to prevent sevoflurane-induced hyperactivity. Results: In the behavioral model, sevoflurane could induce significant hyperactivity in mice under 1% sevoflurane inhalation and in recovery period, characterized as increased movement speed and total distance. The sevoflurane-induced hyperactivity was more significant in young mice than adult (P<0.01). Pre-administration of ZD7288 could significantly prevent sevoflurane-induced hyperactivity. Conclusions: The mice behavioral model developed in this study could characterize sevoflurane-induced hyperactivity in induction and recovery period as well as age-dependence. In addition, by this animal model, HCN channel blocker ZD7288 could prevent sevoflurane-induced hyperactivity. Thus, HCN channel might be the underlying therapeutic target for sevoflurane-induced agitation in general anesthesia.   Citation: Peng Liang, Xu-Bin Huang, Feng-Shan Li, Han Huang, Jing-Xuan Qiu, Da-Qing Liao, et al. Hyperpolarization-activated cyclic nucleotide-gated channel blocker ZD7288 prevents sevoflurane-induced hyperactivity in a novel mice behavioral model. J Anesth Perioper Med 2017; 4: 205-12. doi: 10.24015/JAPM.2017.0011This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI: 10.1213/00000539-198611000-00025
发表时间: 1986-11
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作者:
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期刊: SpringerPlus
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DOI: 10.1097/00001503-200106000-00010
发表时间: 2001-06-01
期刊: Current opinion in anaesthesiology
影响因子: --
作者:
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DOI: 10.1097/aln.0000000000000181
发表时间: 2014-06-01
期刊: ANESTHESIOLOGY
影响因子: 8.8
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