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新冠病毒肺炎患者细胞因子水平、肾脏和心脏功能生物标志物以及血管紧张素转换酶2和神经纤毛蛋白1表达水平之间的关联

The Associations between Cytokine Levels, Kidney and Heart Function Biomarkers, and Expression Levels of Angiotensin-Converting Enzyme-2 and Neuropilin-1 in COVID-19 Patients.

作者信息

Sultan Rabab Hussain, Abdallah Maged, Ali Tarek M, Ahmed Amr E, Assal Hebatallah Hany, Elesawy Basem H, Ahmed Osama M

机构信息

Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62521, Egypt.

Department of Anesthesia and Intensive Care, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.

出版信息

Vaccines (Basel). 2022 Jun 29;10(7):1045. doi: 10.3390/vaccines10071045.

Abstract

BACKGROUND

Higher expression of angiotensin-converting enzyme-2 (ACE-2) in addition to neuropilin-1 (NRP-1) can lead to a cytokine storm which is correlated to higher mortality rate and contributes to the progression of renal diseases and the pathogenesis of coronary heart disease (CHD) in COVID-19 patients.

AIM

We herein sought to examine correlations between cytokine levels, ACE-2 and NRP-1 expression, renal function biomarkers, and cardiac enzymes in COVID-19 patients.

PATIENTS AND METHODS

For the study, 50 healthy subjects and 100 COVID-19 patients were enrolled. Then, confirmed cases of COVID-19 were divided into two groups-those with moderate infection and those with severe infection-and compared to healthy controls. Serum creatinine, urea, CK-MB, LDH, troponin I, IL-1β, IL-4, IL-10, IL-17, and INF-γ levels were estimated. We also studied the gene expression for ACE-2 and NRP-1 in blood samples utilizing quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

All COVID-19 patients demonstrated a significant increase in the levels of serum creatinine, urea, CK-MB, LDH, and troponin I, as well as examined cytokines compared to the healthy controls. Furthermore, ACE-2 mRNA and NRP-1 mRNA expression levels demonstrated a significant increase in both severe and moderate COVID-19 patient groups. In the severe group, serum creatinine and urea levels were positively correlated with IL-10, INF-γ, NRP-1, and ACE-2 expression levels. Moreover, LDH was positively correlated with all the examined cytokine, NRP-1, and ACE-2 expression levels.

CONCLUSION

Deficits in renal and cardiac functions might be attributable to cytokine storm resulting from the higher expression of ACE-2 and NRP-1 in cases of COVID-19.

摘要

背景

除了神经纤毛蛋白-1(NRP-1)外,血管紧张素转换酶2(ACE-2)的高表达可导致细胞因子风暴,这与较高的死亡率相关,并促进COVID-19患者肾脏疾病的进展和冠心病(CHD)的发病机制。

目的

我们在此研究COVID-19患者细胞因子水平、ACE-2和NRP-1表达、肾功能生物标志物与心肌酶之间的相关性。

患者与方法

本研究纳入50名健康受试者和100名COVID-19患者。然后,将确诊的COVID-19病例分为两组——中度感染组和重度感染组——并与健康对照组进行比较。检测血清肌酐、尿素、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肌钙蛋白I、白细胞介素-1β(IL-1β)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、白细胞介素-17(IL-17)和干扰素-γ(INF-γ)水平。我们还利用定量实时聚合酶链反应(qRT-PCR)研究了血样中ACE-2和NRP-1的基因表达。

结果

与健康对照组相比,所有COVID-19患者的血清肌酐、尿素、CK-MB、LDH和肌钙蛋白I水平以及所检测的细胞因子均显著升高。此外,ACE-2 mRNA和NRP-1 mRNA表达水平在重度和中度COVID-19患者组中均显著升高。在重度组中,血清肌酐和尿素水平与IL-10、INF-γ、NRP-1和ACE-2表达水平呈正相关。此外,LDH与所有检测的细胞因子、NRP-1和ACE-2表达水平呈正相关。

结论

COVID-19病例中ACE-2和NRP-1的高表达导致细胞因子风暴,可能是肾脏和心脏功能缺陷的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ceb/9316107/4aeecbafa6a1/vaccines-10-01045-g001.jpg

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