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自闭症谱系障碍中免疫和过敏相互作用的新概念:蛇床子素的分子、抗炎作用。

A novel concept of immunological and allergy interactions in autism spectrum disorders: Molecular, anti-inflammatory effect of osthole.

机构信息

Department of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-719 Olsztyn, Poland.

Department of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-719 Olsztyn, Poland.

出版信息

Int Immunopharmacol. 2019 Jul;72:1-11. doi: 10.1016/j.intimp.2019.01.058. Epub 2019 Apr 3.

DOI:10.1016/j.intimp.2019.01.058
PMID:30953868
Abstract

BACKGROUND

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by Diagnosis and Statistic Manual 5 (DSM-5) as persistent social interaction and communication deficient across multiple contexts. Various immunological findings have been reported in children with ASD, and co-existing allergic problems have been recorded in children diagnosed with ASD. Osthole, the effective component of Chinese traditional medicine, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of osthole on the histamine-induced inflammatory responses in PBMC cells.

METHODS

Peripheral blood mononuclear cells (PBMC's) from children with: (1) ASD group with co-existing allergies/asthma (n = 29); (2) ASD group without allergy/asthma (n = 29); (3) Allergy group (n = 30) and from typically developing age-matched control subjects (n = 28) were stimulated with either histamine, FXF, osthole or mixture of this substances. mRNA COX-2 gene expression, COX-2 production and inhibitory effect of tested substances on COX-2 were assessed after stimulation.

RESULTS

Children with ASD may show either an innate proinflammatory response or increased activity of COX-2 which could display more impaired behavioral profile than children with non-inflamed. This study indicated that COX-2 may be involved in pathogenesis of ASD and/or allergy, and osthole could be used to decrease the effects of COX-2 in inflammation and ASD development. High incidence of allergy in ASD patients may indicate immune dysregulation that could be of relevance to the pathophysiology, symptomatology or neuroimmunology of ASD.

CONCLUSIONS

This study shows that fexofenadine (FXF - antihistamine drug) and osthole exhibit selective COX-2 enzyme inhibitory activity. The selective COX-2 activity of osthole may explain further the anti-inflammatory properties of osthole in relieving congestion in allergic rhinitis, and as distinctive effects between FXF and osthole were observed, individual antihistamines may have different modes of action via the COX enzyme system.

摘要

背景

自闭症谱系障碍(ASD)是一种神经发育障碍,根据诊断和统计手册 5 版(DSM-5),其在多个环境中表现为持续的社交互动和沟通障碍。在患有 ASD 的儿童中已经报道了各种免疫发现,并且在被诊断患有 ASD 的儿童中已经记录了并存的过敏问题。蛇床子素是中药的有效成分,据报道具有抗炎作用。本研究评估了蛇床子素对 PBMC 细胞中组胺诱导的炎症反应的抗炎作用。

方法

来自:(1)伴有过敏/哮喘的 ASD 组(n=29);(2)无过敏/哮喘的 ASD 组(n=29);(3)过敏组(n=30)和年龄匹配的正常对照组(n=28)的儿童外周血单核细胞(PBMC)用组胺、FXF、蛇床子素或这些物质的混合物刺激。刺激后评估 COX-2 基因表达、COX-2 产生以及测试物质对 COX-2 的抑制作用。

结果

患有 ASD 的儿童可能表现出先天的促炎反应或 COX-2 活性增加,这可能比非炎症儿童表现出更受损的行为特征。本研究表明 COX-2 可能参与 ASD 和/或过敏的发病机制,蛇床子素可用于降低 COX-2 在炎症和 ASD 发展中的作用。ASD 患者过敏的高发率可能表明免疫失调,这与 ASD 的病理生理学、症状学或神经免疫学有关。

结论

本研究表明,非索非那定(FXF-抗组胺药)和蛇床子素表现出选择性 COX-2 酶抑制活性。蛇床子素的选择性 COX-2 活性可能进一步解释了蛇床子素在缓解过敏性鼻炎充血方面的抗炎特性,并且由于观察到 FXF 和蛇床子素之间的差异,单独的抗组胺药可能通过 COX 酶系统具有不同的作用模式。

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