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褪黑素受体在大鼠发热性惊厥模型中的作用。

Role of Melatonin Receptors in Hyperthermia-Induced Acute Seizure Model of Rats.

机构信息

Medical Faculty, Department of Physiology, Selcuk University, Konya, Turkey.

Department of Physiology, Meram Medical School, Necmettin Erbakan University, Konya, Turkey.

出版信息

J Mol Neurosci. 2019 Dec;69(4):636-642. doi: 10.1007/s12031-019-01392-y. Epub 2019 Aug 15.

DOI:10.1007/s12031-019-01392-y
PMID:31418115
Abstract

Melatonin is a neurohormone that has anticonvulsant activity in different experimental seizure models including hyperthermic febrile seizure. However, the mechanisms of this effect are not clear at the receptor level. The aim of the study was to determine which melatonin receptors involve in the hyperthermic febrile seizure model. 22-30 days Wistar male rats were used, and in children, it corresponds to 1.5-2 years. Groups were performed as (1) control, (2) ethanol/saline, (3) DMSO, (4) melatonin (MT), (5) MT + luzindole (LUZ), (6) MT + K-185, (7) MT + prazosin (PRZ), (8) MT + LUZ + K-185, (9) MT + LUZ + PRZ, (10) MT + K-185 + PRZ, and (11) MT + LUZ + PRZ + K-185. The hyperthermic febrile seizure pattern was established by keeping the rats in 45 °C hot water, and the latency, duration, and severity of seizures were determined in all groups. MT, LUZ, K-185, and PRZ were given 15, 45, 15, and 30 min before the induction of seizure, respectively. It was observed that melatonin shortened the duration of seizure, reduced the severity, and did not affect latency and that these effects were not completely blocked by receptor antagonists when compared with control, ethanol/saline, and DMSO groups. In conclusion, the fact that the anticonvulsant effect of melatonin is not completely blocked by all melatonin receptor antagonists. We can conclude that a multimodal mechanism may be responsible for the effect of melatonin receptors alone on the anticonvulsant effect of melatonin. It will be useful to design new pharmacological studies to make the subject clear.

摘要

褪黑素是一种神经激素,在包括高热性惊厥在内的不同实验性癫痫模型中具有抗惊厥活性。然而,其受体水平的作用机制尚不清楚。本研究旨在确定哪些褪黑素受体参与高热性惊厥模型。使用 22-30 天龄雄性 Wistar 大鼠,在儿童中相当于 1.5-2 岁。各组分别为(1)对照组,(2)乙醇/盐水,(3)DMSO,(4)褪黑素(MT),(5)MT+Luzindole(LUZ),(6)MT+K-185,(7)MT+Prazosin(PRZ),(8)MT+LUZ+K-185,(9)MT+LUZ+PRZ,(10)MT+K-185+PRZ,和(11)MT+LUZ+PRZ+K-185。通过将大鼠置于 45°C 热水中建立高热性惊厥模式,并在所有组中确定惊厥的潜伏期、持续时间和严重程度。MT、LUZ、K-185 和 PRZ 分别在惊厥诱导前 15、45、15 和 30 分钟给药。结果观察到,褪黑素缩短了惊厥的持续时间,降低了严重程度,且对潜伏期无影响,与对照组、乙醇/盐水和 DMSO 组相比,这些作用并未被受体拮抗剂完全阻断。总之,褪黑素的抗惊厥作用不能被所有褪黑素受体拮抗剂完全阻断。我们可以得出结论,一种多模式机制可能是褪黑素受体单独作用于褪黑素抗惊厥作用的原因。这将有助于设计新的药理学研究,以使该主题更加清晰。

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本文引用的文献

1
Diurnal occurrence of complex febrile seizure and their severity in pediatric patients needing hospitalization.儿科需住院患者复杂热性惊厥的日发作频次及其严重程度。
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Anticonvulsant activity of melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, in mice.
褪黑素而非褪黑素受体激动剂Neu-P11和Neu-P67在小鼠中的抗惊厥活性。
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Anticonvulsant efficacy of melatonin in an experimental model of hyperthermic febrile seizures.褪黑素在高热惊厥实验模型中的抗惊厥疗效。
Epilepsy Res. 2015 Dec;118:49-54. doi: 10.1016/j.eplepsyres.2015.11.004. Epub 2015 Nov 10.
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Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.褪黑素增强苯巴比妥在新生大鼠中的抗惊厥作用。
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Melatonin and its agonists in pain modulation and its clinical application.褪黑素及其激动剂在疼痛调节中的作用及其临床应用。
Arch Ital Biol. 2012 Dec;150(4):274-89. doi: 10.4449/aib.v150i4.1391.
8
Melatonin modulates the GABAergic response in cultured rat hippocampal neurons.褪黑素调节培养的大鼠海马神经元中的 GABA 能反应。
J Pharmacol Sci. 2012;119(2):177-85. doi: 10.1254/jphs.11183fp. Epub 2012 May 31.
9
The neuroprotective effect of topiramate on the ultrastructure of pyramidal neurons of the hippocampal CA1 and CA3 sectors in an experimental model of febrile seizures in rats.托吡酯对发热性癫痫大鼠模型中海马 CA1 和 CA3 区锥体神经元超微结构的神经保护作用。
Folia Neuropathol. 2011;49(3):230-6.
10
The interaction of melatonin and agmatine on pentylenetetrazole-induced seizure threshold in mice.褪黑素和胍丁胺对戊四氮诱导的小鼠癫痫发作阈的相互作用。
Epilepsy Behav. 2011 Oct;22(2):200-6. doi: 10.1016/j.yebeh.2011.07.002. Epub 2011 Aug 15.