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血清促炎细胞因子、核因子 κB 受体激活剂配体(RANKL)、骨保护素(OPG)及 RANKL/OPG 比值在轻症和重症 COVID-19 中的变化。

Serum proinflammatory cytokines, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG ratio in mild and severe COVID-19.

机构信息

Department of Orthopedics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

BMC Infect Dis. 2024 Sep 27;24(1):1047. doi: 10.1186/s12879-024-09941-6.

DOI:10.1186/s12879-024-09941-6
PMID:39333916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11428542/
Abstract

INTRODUCTION

Osteoporosis, a systemic skeletal disease, is characterized by a quantitative and qualitative, and progressive decrease in bone mass, which is related to inflammation. Since a cytokine storm is triggered in Coronavirus disease 2019 (COVID-19), this study aims to evaluate pro-inflammatory cytokines (TNF-α, IL-1β), Receptor activator of nuclear factor-κB ligand (RANKL)/serum osteoprotegerin (OPG) ratio, and their relationship in mild and severe COVID-19.

METHODS

This study was performed on 48 adult patients (18 mild, 18 severe COVID-19, and 12 healthy subjects as a control group). Serum OPG, RANKL, TNF-α, IL-1β, 25-OH vitamin D, and ALKp were measured by ELISA and colorimetric assay.

RESULTS

COVID-19 patients had a significant increase in RANKL, and RANKL/OPG in mild and severe form (p < 0.001) while OPG decreased significantly in severe form compared to healthy controls (p < 0.05). Inflammatory cytokines (TNF-α and IL-1β) increased in both groups of patients whereas Alkaline phosphatase (ALKp) increased only in severe patients (p < 0.001). Both groups had 25-OH vitamin D deficiency in comparison to healthy ones (p < 0.001). Pearson's correlation coefficient was performed to determine the relationship between RANKL, OPG, ALKp, and 25-OH vitamin D with TNF-α and IL-1β in mild and severe COVID-19, which was statistically significant.

CONCLUSION

Serum RANKL/OPG ratio was elevated in COVID-19 individuals and is assumed to be a risk factor for BMD reduction and osteoporosis in these patients. Correlations between IL-1β, TNF-α, ALKp, 25-OH vitamin D, OPG, RANKL, and RANKL/OPG ratio offered the potential role of these proinflammatory markers in the mechanism of osteoporosis in COVID-19 patients.

摘要

简介

骨质疏松症是一种全身性骨骼疾病,其特征是骨量的数量和质量以及进行性下降,这与炎症有关。由于 2019 年冠状病毒病(COVID-19)引发了细胞因子风暴,因此本研究旨在评估促炎细胞因子(TNF-α,IL-1β)、核因子-κB 受体激活剂配体(RANKL)/血清骨保护素(OPG)比值及其与 COVID-19 轻症和重症的关系。

方法

本研究共纳入 48 例成年患者(18 例轻症 COVID-19,18 例重症 COVID-19,12 例健康对照)。采用酶联免疫吸附法和比色法测定血清 OPG、RANKL、TNF-α、IL-1β、25-羟维生素 D 和 ALKp。

结果

COVID-19 患者的 RANKL 和 RANKL/OPG 在轻症和重症中均显著升高(p<0.001),而 OPG 在重症中与健康对照组相比显著降低(p<0.05)。两组患者的炎症细胞因子(TNF-α和 IL-1β)均升高,而 ALKp 仅在重症患者中升高(p<0.001)。与健康对照组相比,两组患者均存在 25-羟维生素 D 缺乏(p<0.001)。在 COVID-19 轻症和重症患者中,进行了 Pearson 相关系数分析,以确定 RANKL、OPG、ALKp 和 25-羟维生素 D 与 TNF-α和 IL-1β之间的关系,结果具有统计学意义。

结论

COVID-19 患者血清 RANKL/OPG 比值升高,被认为是这些患者 BMD 降低和骨质疏松的危险因素。IL-1β、TNF-α、ALKp、25-羟维生素 D、OPG、RANKL 和 RANKL/OPG 比值之间的相关性表明这些促炎标志物在 COVID-19 患者骨质疏松发病机制中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/1f69d5e28872/12879_2024_9941_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/cd7e7dff1ca7/12879_2024_9941_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/236cac567edf/12879_2024_9941_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/4f3e04184368/12879_2024_9941_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/1f69d5e28872/12879_2024_9941_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/cd7e7dff1ca7/12879_2024_9941_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/236cac567edf/12879_2024_9941_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/4f3e04184368/12879_2024_9941_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbfa/11428542/1f69d5e28872/12879_2024_9941_Fig4_HTML.jpg

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