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衰老仓鼠感染严重急性呼吸综合征冠状病毒 2 后的异常凝血和肾脏损伤。

Abnormal Blood Coagulation and Kidney Damage in Aged Hamsters Infected with Severe Acute Respiratory Syndrome Coronavirus 2.

机构信息

Laboratory for Biologics Development, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.

Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.

出版信息

Viruses. 2021 Oct 22;13(11):2137. doi: 10.3390/v13112137.

Abstract

Systemic symptoms have often been observed in patients with coronavirus disease 2019 (COVID-19) in addition to pneumonia, however, the details are still unclear due to the lack of an appropriate animal model. In this study, we investigated and compared blood coagulation abnormalities and tissue damage between male Syrian hamsters of 9 (young) and over 36 (aged) weeks old after intranasal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite similar levels of viral replication and inflammatory responses in the lungs of both age groups, aged but not young hamsters showed significant prolongation of prothrombin time and prominent acute kidney damage. Moreover, aged hamsters demonstrated increased intravascular coagulation time-dependently in the lungs, suggesting that consumption of coagulation factors causes prothrombin time prolongation. Furthermore, proximal urinary tract damage and mesangial matrix expansion were observed in the kidneys of the aged hamsters at early and later disease stages, respectively. Given that the severity and mortality of COVID-19 are higher in elderly human patients, the effect of aging on pathogenesis needs to be understood and should be considered for the selection of animal models. We, thus, propose that the aged hamster is a good small animal model for COVID-19 research.

摘要

除了肺炎,新型冠状病毒病 2019(COVID-19)患者还常出现全身症状,但由于缺乏合适的动物模型,其具体情况仍不清楚。在这项研究中,我们研究并比较了 9 周龄(年轻)和 36 周龄(年老)的雄性叙利亚仓鼠经鼻腔感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)后的凝血异常和组织损伤。尽管两个年龄段的仓鼠肺部的病毒复制和炎症反应相似,但只有年老的仓鼠而非年轻的仓鼠出现明显的凝血酶原时间延长和显著的急性肾损伤。此外,年老的仓鼠肺部的血管内凝血时间依赖性延长,提示凝血因子的消耗导致凝血酶原时间延长。此外,在疾病的早期和晚期阶段,年老仓鼠的肾脏分别出现近端尿路损伤和肾小球系膜基质扩张。鉴于 COVID-19 在老年患者中的严重程度和死亡率更高,需要了解衰老对发病机制的影响,并应考虑选择动物模型。因此,我们提出年老仓鼠是 COVID-19 研究的良好小型动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d537/8618556/d705323db62a/viruses-13-02137-g001.jpg

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