背景:代谢失调和过度炎症与2019年冠状病毒病(COVID-19)的高度传染性疾病的发病机理有关,这是由一种新出现的冠状病毒引起的(即,严重急性呼吸综合征-冠状病毒2;SARS-CoV-2)。腺苷5'-单磷酸活化蛋白激酶(AMPK),一种调节不同细胞代谢途径的能量传感器,在免疫系统中发挥调节作用。本研究旨在检测不同级别COVID-19患者AMPKmRNA表达水平以及血浆白细胞介素-6(IL-6)和IL-10细胞因子水平。
方法:收集60例COVID-19(中度,严重,和关键)。采用酶联免疫吸附试验(ELISA)检测血浆IL-6和IL-10水平,实时荧光定量PCR检测AMPK的mRNA表达水平。
结果:结果显示,与COVID-19的中度病例相比,重症和重症患者的血浆IL-6水平显着升高(P<0.001)。此外,重症和危重病例IL-10血浆浓度明显高于中度病例(P<0.01和P<0.05)。此外,相对于COVID-19的中度和重度病例,重症患者中AMPK的基因表达明显增强(分别为P<0.001和P<0.01)。AMPK基因表达与血浆IL-6和IL-10水平呈正相关(P=0.006,r=0.348,P=0.028,r=0.283)。
结论:增加AMPK基因表达可能是免疫系统抑制危重COVID-19炎症的必要努力。然而,这种努力似乎是不够的,可能是由于诱发炎症的因素,如红细胞沉降率(ESR)和IL-6。
BACKGROUND: Metabolic dysregulation and excessive inflammation are implicated in the pathogenesis of the highly infectious disease of coronavirus disease 2019 (COVID-19), which is caused by a newly emerging coronavirus (i.e., severe acute respiratory syndrome-coronavirus 2; SARS-CoV-2). The adenosine 5\'-monophosphate-activated protein kinase (AMPK), an energy sensor regulating the metabolic pathways in diverse cells, exerts a regulatory role in the immune system. This study aims to examine the mRNA expression level of AMPK and the plasma levels of interleukin-6 (IL-6) and IL-10 cytokines in patients with different grades of COVID-19.
METHODS: Peripheral blood was collected from 60 patients with COVID-19 (Moderate, severe, and critical). The plasma levels of IL-6 and IL-10 were quantified by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression level of AMPK was determined using real-time PCR.
RESULTS: The results showed that the plasma levels of IL-6 increased significantly in critical and severe patients compared to moderate cases of COVID-19 (P < 0.001). Moreover, IL-10 plasma concentrations were significantly higher in critical and severe cases than in moderate cases of COVID-19 (P < 0.01 and P < 0.05, respectively). Also, the gene expression of AMPK was meaningfully enhanced in critical patients relative to moderate and severe cases of COVID-19, in order (P < 0.001 and P < 0.01, respectively). There was a positive association between AMPK gene expression and plasma levels of IL-6 and IL-10 (P = 0.006, r = 0.348, P = 0.028, r = 0.283, respectively).
CONCLUSIONS: Increasing AMPK gene expression is likely a necessary effort of the immune system to inhibit inflammation in critical COVID-19. However, this effort seems to be inadequate, probably due to factors that induce inflammation, like erythrocyte sedimentation rate (ESR) and IL-6.