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中性粒细胞弹性蛋白酶 (NE) 酶与炎症在 2019 年冠状病毒病 (COVID-19) 发病机制中的可能致病相关性。

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19).

机构信息

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Middle East Liver Diseases (MELD) Center, Tehran, Iran.

出版信息

Int Immunopharmacol. 2021 Nov;100:108137. doi: 10.1016/j.intimp.2021.108137. Epub 2021 Sep 14.

Abstract

A growing body of evidence indicates that neutrophil elastase (NE) is involved in the pathogenesis of respiratory infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to analyze the dynamic changes in serum levels of NE associated with inflammation, disease activity, and mortality rate in patients with COVID-19. We measured the serum concentrations of NE, C-Reactive protein (CRP), interleukin (IL)- 4, IL-6, IL-8, IL-10, and vitamin D levels in 83 ICU and 69 non-ICU patients compared with 82 healthy subjects (HS) in three-time points (T1-T3). Serum levels of NE, IL-6, IL-8, and CRP in ICU and non-ICU patients were significantly higher than HS (P < 0.001) in three-time points. Also, serum levels of NE, IL-6, IL-8, and CRP in ICU patients were significantly higher than in non-ICU patients (P < 0.05). On the day of admission (T1), the levels of NE, CRP, IL-6, IL-8 were gradually decreased from T1 to T3. At the same time, IL-4 and IL-10 were gradually increased from T1 to T2 and then reduced to T3. Further analyses demonstrated that the levels of NE, IL-6, and IL-8 in deceased patients were significantly higher than in recovered patients (P < 0.05). The ROC curve analysis demonstrated that markers, including NE, IL-6, and IL-8, were valuable indicators in evaluating the activity of COVID-19. Overall, our results signify the critical role of NE in the pathogenesis of COVID-19, and also, further support that NE has a potential therapeutic target for the attenuation of COVID-19 severity.

摘要

越来越多的证据表明,中性粒细胞弹性蛋白酶(NE)参与了呼吸道传染病的发病机制,例如严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)。本研究旨在分析与 COVID-19 患者炎症、疾病活动度和死亡率相关的血清 NE 水平的动态变化。我们在三个时间点(T1-T3)测量了 83 例 ICU 患者和 69 例非 ICU 患者以及 82 例健康对照者(HS)的血清 NE、C 反应蛋白(CRP)、白细胞介素(IL)-4、IL-6、IL-8、IL-10 和维生素 D 水平。ICU 和非 ICU 患者的血清 NE、IL-6、IL-8 和 CRP 水平在三个时间点均显著高于 HS(P<0.001)。此外,ICU 患者的血清 NE、IL-6、IL-8 和 CRP 水平也显著高于非 ICU 患者(P<0.05)。入院当天(T1),NE、CRP、IL-6、IL-8 水平从 T1 逐渐下降至 T3。与此同时,IL-4 和 IL-10 从 T1 逐渐增加到 T2,然后减少到 T3。进一步分析表明,死亡患者的 NE、IL-6 和 IL-8 水平明显高于恢复患者(P<0.05)。ROC 曲线分析表明,NE、IL-6 和 IL-8 等标志物是评估 COVID-19 活动度的有价值指标。总体而言,我们的研究结果表明 NE 在 COVID-19 的发病机制中具有关键作用,同时也进一步支持 NE 可能是降低 COVID-19 严重程度的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e9/8437823/784c9f159084/gr1_lrg.jpg

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