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NLRP3 炎性体在肥胖症和 PCOS 中的作用:系统评价和荟萃分析。

The Role of NLRP3 Inflammasome in Obesity and PCOS-A Systematic Review and Meta-Analysis.

机构信息

Division of Translational Medical Sciences, School of Medicine, Royal Derby Hospital Centre, University of Nottingham, Derby DE22 3DT, UK.

Prince Mohammed Bin Abdulaziz Medical City, Ministry of Health, Riyadh 14214, Saudi Arabia.

出版信息

Int J Mol Sci. 2023 Jul 1;24(13):10976. doi: 10.3390/ijms241310976.

Abstract

Inflammasomes have recently been implicated in the pathogenesis of several chronic inflammatory disorders, such as diabetes and obesity. The aim of this meta-analysis was to investigate the possible role of the NLRP3 inflammasome in obesity and polycystic ovarian syndrome (PCOS). A comprehensive search of electronic databases was conducted to identify studies investigating NLRP3 its related components (Caspase 1, ASC and IL-1β) in adipose tissue and/or blood from obese individuals compared to non-obese controls. Another search was conducted for studies investigating NLRP3 in PCOS women and animal models. The ssearched databases included Medline, EMBASE, Cochrane Library, PubMed, Clinicaltrials.gov, the EU Clinical Trials Register and the WHO International Clinical Trials Register. The quality and risk of bias for the included articles were assessed using the modified Newcastle-Ottawa scale. Data were extracted and pooled using RevMan software for the calculation of the standardized mean difference (SMD) and 95% confidence interval (CI). Twelve eligible studies were included in the obesity systematic review and nine in the PCOS review. Of the obesity studies, nine ( = 270) were included in the meta-analysis, which showed a significantly higher adipose tissue NLRP3 gene expression in obese ( = 186) versus non-obese ( = 84) participants (SMD 1.07; 95% CI, 0.27, 1.87). Pooled analysis of adipose tissue IL-1β data from four studies showed significantly higher IL-1β gene expression levels in adipose tissue from 88 obese participants versus 39 non-obese controls (SMD 0.56; 95% CI, 0.13, 0.99). Meta-analysis of adipose tissue ASC data from four studies showed a significantly higher level in obese ( = 109) versus non-obese ( = 42) individuals (SMD 0.91, 95% CI, 0.30, 1.52). Of the nine PCOS articles, three were human ( = 185) and six were animal studies utilizing PCOS rat/mouse models. All studies apart from one article consistently showed upregulated NLRP3 and its components in PCOS women and animal models. In conclusion, obesity and PCOS seem to be associated with upregulated expression of NLRP3 inflammasome components. Further research is required to validate these findings and to elucidate the role of NLRP3 in obesity and PCOS.

摘要

炎症小体最近被认为与几种慢性炎症性疾病的发病机制有关,如糖尿病和肥胖症。本荟萃分析的目的是研究 NLRP3 炎症小体在肥胖症和多囊卵巢综合征(PCOS)中的可能作用。通过全面检索电子数据库,确定了研究 NLRP3 及其相关成分(半胱天冬酶 1、ASC 和 IL-1β)在肥胖个体与非肥胖对照者的脂肪组织和/或血液中的作用的研究。还对研究 NLRP3 在 PCOS 女性和动物模型中的作用的研究进行了另一项检索。所检索的数据库包括 Medline、EMBASE、Cochrane 图书馆、PubMed、Clinicaltrials.gov、欧盟临床试验注册处和世界卫生组织国际临床试验注册平台。使用改良的 Newcastle-Ottawa 量表评估纳入文章的质量和偏倚风险。使用 RevMan 软件提取和汇总数据,以计算标准化均数差(SMD)和 95%置信区间(CI)。肥胖症系统评价纳入了 12 项研究,多囊卵巢综合征评价纳入了 9 项研究。在肥胖症研究中,有 9 项(=270)纳入了荟萃分析,结果表明,肥胖者(=186)的脂肪组织 NLRP3 基因表达明显高于非肥胖者(=84)(SMD1.07;95%CI,0.27,1.87)。对四项研究中脂肪组织 IL-1β 数据的汇总分析显示,与 39 名非肥胖对照组相比,88 名肥胖参与者的脂肪组织中 IL-1β 基因表达水平明显更高(SMD0.56;95%CI,0.13,0.99)。对四项研究中脂肪组织 ASC 数据的荟萃分析显示,肥胖者(=109)的 ASC 水平明显高于非肥胖者(=42)(SMD0.91,95%CI,0.30,1.52)。在 9 项 PCOS 研究中,有 3 项为人类研究(=185),6 项为 PCOS 大鼠/小鼠模型的动物研究。除了一篇文章外,所有其他文章均一致表明,PCOS 女性和动物模型中 NLRP3 及其成分的表达上调。需要进一步研究来验证这些发现,并阐明 NLRP3 在肥胖症和 PCOS 中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6843/10341879/6bdc81e3cb9b/ijms-24-10976-g001.jpg

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