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精神分裂症患者外周血单个核细胞中 NLRP3 炎性小体表达增加:一项病例对照研究。

Increased NLRP3 inflammasome expression in peripheral blood mononuclear cells of patients with schizophrenia: a case-control study.

机构信息

Department of Psychiatry, Suleyman Demirel University, Faculty of Medicine, Isparta, Turkey.

Department of Medical Genetics, Suleyman Demirel University, Faculty of Medicine, Isparta, Turkey.

出版信息

Int J Psychiatry Clin Pract. 2023 Jun;27(2):111-117. doi: 10.1080/13651501.2022.2106245. Epub 2022 Aug 6.

DOI:10.1080/13651501.2022.2106245
PMID:35938405
Abstract

OBJECTIVE

This study aimed to evaluate the gene expression of the P2X purinoceptor 7 (P2X7R)- nod-like receptor pyrin domain-containing protein 3 (NLRP3) signal pathway in peripheral blood mononuclear cells (PBMCs) between schizophrenia (SCZ) patients and healthy controls (HC) to reveal its relationship with clinical variables.

METHODS

Thirty-two SCZ patients and 41 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS), The Global Assessment of Functioning (GAF) scale and the Functioning Assessment Short Test (FAST) scales were applied. P2X7R, NLRP3, IL-1β and IL-18 gene expression levels were evaluated by real-time polymerase chain reaction in PBMCs.

RESULTS

NLRP3, P2RX7, IL-1β and IL-18 expression levels were significantly higher in PBMCs of SCZ patients than in HC subjects. Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores. There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores and a positive correlation with the SAPS scale scores.

CONCLUSIONS

Systemic inflammation is implicated in SCZ pathogenesis, according to our findings, which suggest that the NLRP3 pathway may be involved. The NLRP3 inflammasome may serve as a biomarker for SCZ, and its pharmacological regulation may be a promising treatment approach.Key pointsWe hypothesised that the NLRP3 pathway may contribute to the etiopathogenesis of schizophrenia.NLRP3, IL-1β and IL-18 mRNA levels were higher in patients with schizophrenia compared to healthy controls.Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores.There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores.The SAPS scale scores and IL-18 expression levels had a positive correlation.Given all these findings, it can be stated that NLRP3 inflammasome may play a role in the pathogenesis and symptoms of schizophrenia.

摘要

目的

本研究旨在评估精神分裂症(SCZ)患者与健康对照(HC)外周血单个核细胞(PBMCs)中 P2X7 嘌呤能受体(P2X7R)-NOD 样受体热蛋白结构域包含蛋白 3(NLRP3)信号通路的基因表达,以揭示其与临床变量的关系。

方法

本研究纳入 32 例 SCZ 患者和 41 例健康对照。采用阳性症状评定量表(SAPS)和阴性症状评定量表(SANS)、总体功能评估量表(GAF)和功能评估快速测试量表(FAST)进行评估。采用实时聚合酶链反应(PCR)检测 PBMCs 中 P2X7R、NLRP3、IL-1β和 IL-18 基因的表达水平。

结果

与 HC 相比,SCZ 患者的 PBMCs 中 NLRP3、P2RX7、IL-1β和 IL-18 的表达水平显著升高。NLRP3 基因表达水平与 GAF 和 FAST 评分呈负相关。IL-18 表达水平与 GAF 和 FAST 评分呈负相关,与 SAPS 评分呈正相关。

结论

根据我们的研究结果,全身炎症与精神分裂症的发病机制有关,这表明 NLRP3 通路可能参与其中。NLRP3 炎性小体可能是精神分裂症的生物标志物,其药理学调节可能是一种有前途的治疗方法。

关键点

我们假设 NLRP3 通路可能导致精神分裂症的发病机制。与健康对照组相比,精神分裂症患者的 NLRP3、IL-1β 和 IL-18 mRNA 水平较高。NLRP3 基因表达水平与 GAF 和 FAST 评分呈负相关。IL-18 表达水平与 GAF 和 FAST 评分呈负相关,与 SAPS 评分呈正相关。

综上所述,NLRP3 炎性小体可能在精神分裂症的发病机制和症状中起作用。

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