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维生素D结合蛋白:老年COVID-19急性肺损伤的一个潜在因素。

Vitamin D Binding Protein: A Potential Factor in Geriatric COVID-19 Acute Lung Injury.

作者信息

Jiang Hongjuan, Chi Xiangyu, Sun Yanhong, Li Hongwen

机构信息

Department of Geriatric Respiratory Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.

出版信息

J Inflamm Res. 2024 Jul 8;17:4419-4429. doi: 10.2147/JIR.S470097. eCollection 2024.

Abstract

BACKGROUND

Previous research indicated that vitamin D binding protein (VDBP) is an independent multifunctional protein that plays a vital role in acute inflammatory and tissue damage. However, its role in acute lung injury (ALI) due to coronavirus disease 2019 (COVID-19) is unclear, and studies are lacking. This study intends to investigate the difference in serum VDBP levels in COVID-19 patients with ALI or without ALI and further explore the role of VDBP in the inflammatory response of ALI through cellular models.

METHODS

The serum was collected from COVID-19 patients, and the concentration of serum VDBP was detected. Construct a VDBP gene-silencing plasmid and transfect it into human alveolar epithelial A549 cells. After 72 hours of lipopolysaccharide (LPS) intervention, The inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected, and cell counting kit-8 (CCK-8) assay was used to detect cell viability. Flow cytometry was used to detect cell apoptosis.

RESULTS

The serum concentration of VDBP was significantly higher in COVID-19 with ALI ( < 0.05). Correlation analysis indicated serum VDBP positively correlated with leukocyte (=0.329, = 0.002), c-reaction protein ( = 0.470, < 0.001), serum amyloid A ( = 0.900, < 0.001), procalcitonin ( = 0.670, < 0.001), and interleukin 6 ( = 0.452, < 0.001). Simultaneously, the logistic regression analysis showed that increased serum VDBP was an independent risk factor for ALI in COVID-19 patients (OR 1.003 95% CI 1.001-1.006, = 0.002). In human alveolar epithelial A549 cells, after LPS intervention, the inflammatory factor IL-1β and TNF-A significantly reduced in the VDBP gene silencing group compared to the negative control (NC) group ( < 0.05). The cell viability of the VDBP gene silencing group was significantly increased compared to the NC group, and the cell apoptosis rate was significantly reduced ( < 0.05).

CONCLUSION

In COVID-19 patients, acute lung injury may lead to increased serum concentration of VDBP. VDBP plays a vital role in promoting inflammatory response and apoptosis of bronchial epithelial cells.

摘要

背景

先前的研究表明,维生素D结合蛋白(VDBP)是一种独立的多功能蛋白,在急性炎症和组织损伤中起重要作用。然而,其在2019冠状病毒病(COVID-19)所致急性肺损伤(ALI)中的作用尚不清楚,且相关研究较少。本研究旨在调查COVID-19合并ALI或未合并ALI患者血清VDBP水平的差异,并通过细胞模型进一步探讨VDBP在ALI炎症反应中的作用。

方法

收集COVID-19患者的血清,检测血清VDBP浓度。构建VDBP基因沉默质粒并转染至人肺泡上皮A549细胞。脂多糖(LPS)干预72小时后,检测炎症因子白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α),并采用细胞计数试剂盒-8(CCK-8)法检测细胞活力。采用流式细胞术检测细胞凋亡。

结果

COVID-19合并ALI患者血清VDBP浓度显著升高(<0.05)。相关性分析表明,血清VDBP与白细胞(=0.329,=0.002)、C反应蛋白(=0.470,<0.001)、血清淀粉样蛋白A(=0.900,<0.001)、降钙素原(=0.670,<0.001)和白细胞介素6(=0.452,<0.001)呈正相关。同时,逻辑回归分析显示,血清VDBP升高是COVID-19患者发生ALI的独立危险因素(OR 1.003 95%CI 1.001-1.006,=0.002)。在人肺泡上皮A549细胞中,LPS干预后,VDBP基因沉默组的炎症因子IL-1β和TNF-A较阴性对照组(NC)显著降低(<0.05)。VDBP基因沉默组的细胞活力较NC组显著升高,细胞凋亡率显著降低(<0.05)。

结论

在COVID-19患者中,急性肺损伤可能导致血清VDBP浓度升高。VDBP在促进支气管上皮细胞炎症反应和凋亡中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21ad/11244632/78009d101d34/JIR-17-4419-g0001.jpg

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