Science子刊:为什么某些新冠肺炎患者症状更严重?高血糖水平或可解释

2020-04-20 于晓程 生物探索

随着新冠肺炎疫情在全球范围蔓延,医务工作者和科研人员注意到,糖尿病患者的预后往往比没有潜在健康问题的人更差,这与流感感染相同。武汉大学等多家科研机构的研究人员试图更好地理解为什么这些病人更容易受到炎症

随着新冠肺炎疫情在全球范围蔓延,医务工作者和科研人员注意到,糖尿病患者的预后往往比没有潜在健康问题的人更差,这与流感感染相同。武汉大学等多家科研机构的研究人员试图更好地理解为什么这些病人更容易受到炎症反应的影响,从而导致肺炎和死亡,他们在小鼠模型和流感患者中开展工作,发现高血糖水平或许可以解释这一问题,相关论文发表在《Science Advances》杂志上。

先前的研究表明,当流感病毒(或SARS-CoV-2病毒)进入人体时,免疫系统的反应是将免疫细胞送到该部位以对抗威胁,细胞因子是作为反应的一部分而产生,它们的工作是处理细胞间通信。然而,某些人产生的细胞因子过多,造成细胞因子风暴,这可能会导致非常严重的问题,如肺炎或器官衰竭,科学家还不清楚为什么有些病人会出现这种情况,而其他病人却不会。在这项新的研究中,研究人员怀疑血液中葡萄糖水平的升高可能起了作用,于是给流感感染的小鼠注射了葡萄糖胺,以观察其是否会导致细胞因子风暴几率的增加,结果发现确实如此。


GlcN增强A型流感病毒(IAV)诱导的炎症细胞因子表达

该研究的另一部分涉及在疫情爆发之前,对中国武汉两家医院的119名流感患者的血液样本进行分析,并与健康人的血液进行了比较,发现IAV感染患者中较高的促炎细胞因子水平与较高的血糖水平相关。研究人员还确定了其中的分子机制,IAV诱导O-GlcNAc转移酶(OGT)与干扰素调节因子5(IRF5)结合,导致IRF5在丝氨酸430上的糖基化,而IRF5的K63位泛素化以及随后的细胞因子产生都需要IRF5糖基化,突出了IAV诱导的细胞因子风暴中葡萄糖代谢的重要性。


分析IAV感染患者的葡萄糖水平、炎性细胞因子表达和IRF5糖基化水平

这项研究解释了为什么糖尿病患者更有可能经历细胞因子风暴,并因流感病毒(或SARS-CoV-2病毒)感染而导致更差的结果。尽管还需要更多的研究来了解病毒诱导的细胞因子风暴和葡萄糖代谢之间微妙的调控机制,但目前的发现可能为未来治疗病毒感染提供一个潜在的靶点。

原始来源:
Qiming Wang1, et al. O-GlcNAc transferase promotes influenza A virus–induced cytokine storm by targeting interferon regulatory factor–5. Science Advances 15 Apr 2020:

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    2020-04-22 hbwxf
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    2020-04-22 jichang
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    2020-04-21 常春藤0702

    0

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    2020-04-20 公卫新人

    新冠肺炎,疫情何时才能消失

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