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关于COVID-19最新假设:缓激肽风暴(GT+correction)

已有 1222 次阅读 2020-9-3 09:17 |个人分类:Health & Health-Care System|系统分类:科普集锦| Bradykinin Storm, COVID-19

昨天才看到的报道。用谷狗翻译后,略加修改 (为了便于阅读)。

Is a Bradykinin Storm Brewing in COVID-19?

是缓激肽风暴在COVID-19患者体内酝酿吗?

 

Excess of the inflammatory molecule bradykinin may explain the fluid build-up in the lungs of patients with coronavirus infections. Clinical trials of inhibitors are putting this hypothesis to the test.


过量炎性分子缓激肽 可解释冠状病毒感染患者肺部积液。抑制剂的临床试验正在检验这一假设。

 

 

Alakananda Dasgupta
Aug 26, 2020

 

On a Sunday afternoon in mid-April this year, Daniel Jacobson, a computational systems biologist at Oak Ridge National Laboratory in Tennessee, was looking at gene expression data from the lung fluid of COVID-19 patients on his computer screen when he spotted something striking—the expression of genes for key enzymes in the renin-angiotensin system (RAS), involved in blood pressure regulation and fluid balance, was askew.


在今年四月中旬的一个星期天下午,田纳西州橡树岭国家实验室的计算系统生物学家丹尼尔·雅各布森在计算机屏幕上查看COVID-19患者肺液的基因表达数据时发现了一些惊人的现象:涉及血压调节和体液平衡的肾素-血管紧张素系统(RAS)中 关键酶基因的表达是歪斜(askew)的。

 

Jacobson followed this abnormal RAS in the lung fluid samples to the kinin cascade, an inflammatory pathway that is tightly regulated by the RAS. He found that the kinin system—in which a key peptide, bradykinin, causes blood vessels to leak and fluid to accumulate in tissues and organs—was thrown out of balance as well in COVID-19 patients. Infected individuals showed heightened expression of genes for the bradykinin receptors, as well as for enzymes called kallikreins that activate the kinin pathway, compared with controls.

雅各布森(Jacobson)跟踪 肺液样本中的这种异常RAS,发现 激肽级联反应,这是一种由RAS严格调节的炎性途径。他发现 激肽系统(其中关键肽缓激肽导致血管渗漏和组织和器官中积聚的液体)在COVID-19患者中也失去了平衡。与对照组相比,被感染的个体显示出缓激肽受体以及激活激肽途径的激肽释放酶基因的表达增加。

 

The results, published July 7 in eLife, could perhaps explain the abnormal accumulation of fluid in the lungs that is so common in COVID-19 patients, the authors say.


这组结果发表在7月7日的eLife。它们也许可以解释COVID-19患者肺部积水异常的现象。

 

Unbeknownst to Jacobson, Frank van de Veerdonk, an infectious disease specialist at the Radboud University Medical Center in the Netherlands, was heading down the same molecular pathway in mid-March. He had noticed two features in COVID-19 patients in his clinic—fluid in the lungs and inflammation. Because other labs had pegged angiotensin-converting enzyme-2 (ACE2), a key enzyme in the RAS, as being the SARS-CoV-2 receptor, and because he knew that ACE2 regulates the kinin system, van de Veerdonk began connecting the dots. In April, he and his group hypothesized that a dysregulated bradykinin system was leading to leaky blood vessels in the lungs and perhaps causing excess fluid to build up.

雅各布森并不知道,荷兰拉德布德大学医学中心的传染病专家弗兰克·范·德·维登克(Frank van de Veerdonk)在3月中旬探索过同一分子途径。在他的诊所中,他注意到了COVID-19患者的两个特征 :肺里的液体和炎症。由于其他实验室已将RAS中的关键酶血管紧张素转换酶2(ACE2)钉为SARS-CoV-2受体,并且因为他知道ACE2调节激肽系统,所以van de Veerdonk开始将这些点连接起来。在四月份,他和他的小组提出了一个假设:缓激肽系统失调会导致肺部血管渗漏,并可能导致积聚过多的液体。

 

Josef Penninger, director of the Life Sciences Institute at the University of British Columbia in Vancouver who discovered that ACE2 is the essential in vivo receptor for SARS, tells The Scientist that he is convinced that bradykinin plays a role in COVID-19 pathogenesis. “It does make a lot of sense.”

温哥华不列颠哥伦比亚大学生命科学研究所所长约瑟夫·彭宁纳(Josef Penninger)发现ACE2是SARS的必需体内受体,他对《科学》杂志的科学家说,他确信缓激肽在COVID-19发病机理中发挥了作用。 “这确实很能说服人。”

 

He adds that Jacobson’s study lends support to the hypothesis, but further confirmation is needed. “Gene expression signatures don’t tell us the whole story. I think it is very important to actually measure the proteins.”

他补充说,雅各布森的研究为这一假设提供了支持,但还需要进一步证实。 “基因表达现象不能告诉我们整个故事。我认为实际测量蛋白质非常重要。”

 

van de Veerdonk recognizes that peptide levels need to be measured and is currently setting up mass spectrometry to measure kinins in the plasma, which have a half-life in plasma of just a few seconds.

van de Veerdonk认识到需要测量肽水平,目前正在建立质谱法来测量血浆激肽。血浆激肽的半衰期仅为几秒钟。

 

In the meantime, Jacobson and his coauthors advocate in their paper for targeting the bradykinin pathway to counter the excess fluid present in the lungs of COVID-19 patients. As there are already a couple of approved drugs that can interfere with the kinin pathway, doctors have begun deploying them in a number of clinical trials.

同时,雅各布森和他的共同作者在他们的论文中主张将缓激肽途径作为目标,以抵抗COVID-19患者肺部存在的多余液体。由于已经有几种批准的药物可以干扰激肽途径,因此医生已经开始在许多临床试验中使用它们。

 

https://www.the-scientist.com/news-opinion/is-a-bradykinin-storm-brewing-in-covid-19--67876




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