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褪黑素对单纯月经性偏头痛患者降钙素基因相关肽及某些促炎介质基因表达的影响

The effect of melatonin on gene expression of calcitonin gene-related peptide and some proinflammatory mediators in patients with pure menstrual migraine.

作者信息

Ansari Mohammad, Karkhaneh Azam, Kheirollahi Asma, Emamgholipour Solaleh, Rafiee Mohammad Hessam

机构信息

Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Reference Laboratory, Social Security Organization, Tehran, Iran.

出版信息

Acta Neurol Belg. 2017 Sep;117(3):677-685. doi: 10.1007/s13760-017-0803-x. Epub 2017 Jun 5.

DOI:10.1007/s13760-017-0803-x
PMID:28584969
Abstract

The neuropeptide calcitonin gene-related peptide (CGRP), a potent vasoactive and a marker of trigeminal inflammation, has been considered as an important mediator in various types of migraine such as pure menstrual migraine. Earlier studies have shown that CGRP can modulate the synthesis and release of other inflammatory factor including nitric oxide (NO) and interleukin-1beta (IL-1β) from trigeminal ganglion glial cells. Exogenous melatonin protects the tissues from inflammatory damages. The goal of this study was to determine the anti-inflammatory effects of melatonin on the CGRP expression, inducible nitric oxide synthase (iNOS) activity, NO, and IL-1β release in cultured peripheral blood mononuclear cells (PBMCs) from pure menstrual migraine patients and healthy subjects. This study was performed on 12 pure menstrual migraine patients and 12 age-and sex-matched healthy subjects. PBMCs were isolated and treated with melatonin for 12 h at pharmacological dose. Gene expression was evaluated by real-time PCR. CGRP and IL-1β proteins in culture supernatant were determined by ELISA method. iNOS activity in PBMCs was determined by colorimetric assays. Total nitrite as an indicator of NO concentrations in the culture supernatants was measured using Griess method. We found that melatonin treatment significantly decreases mRNA expression of CGRP release, NO production, and iNOS activity in the patient groups. Taken together, it appears that melatonin reduces inflammation through decreasing CGRP level and iNOS activity in the patients with migraine; however, further studies are needed in this regard.

摘要

神经肽降钙素基因相关肽(CGRP)是一种强效血管活性物质,也是三叉神经炎症的标志物,被认为是包括单纯月经性偏头痛在内的各类偏头痛的重要介质。早期研究表明,CGRP可调节三叉神经节神经胶质细胞中包括一氧化氮(NO)和白细胞介素-1β(IL-1β)在内的其他炎症因子的合成与释放。外源性褪黑素可保护组织免受炎症损伤。本研究的目的是确定褪黑素对来自单纯月经性偏头痛患者和健康受试者的培养外周血单核细胞(PBMC)中CGRP表达、诱导型一氧化氮合酶(iNOS)活性、NO及IL-1β释放的抗炎作用。本研究对12例单纯月经性偏头痛患者和12例年龄及性别匹配的健康受试者进行。分离PBMC并用褪黑素以药理剂量处理12小时。通过实时PCR评估基因表达。用ELISA法测定培养上清液中的CGRP和IL-1β蛋白。用比色法测定PBMC中的iNOS活性。使用格里斯方法测量作为培养上清液中NO浓度指标的总亚硝酸盐。我们发现,褪黑素处理显著降低了患者组中CGRP释放、NO产生和iNOS活性的mRNA表达。综上所述,褪黑素似乎通过降低偏头痛患者的CGRP水平和iNOS活性来减轻炎症;然而,在这方面还需要进一步研究。

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