Wirz Katrin, Schulz Claudia, Söbbeler Franz, Armando Federico, Beythien Georg, Gerhauser Ingo, de Buhr Nicole, Pilchová Veronika, Meyer Zu Natrup Christian, Baumgärtner Wolfgang, Kästner Sabine, von Köckritz-Blickwede Maren
Research Center for Emerging Infections and Zoonoses.
Institute of Biochemistry.
Am J Respir Cell Mol Biol. 2024 Aug;71(2):146-153. doi: 10.1165/rcmb.2024-0005MA.
Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and after inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen concentrations generated . Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. By way of analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection than are young animals. To investigate oxygen concentrations during a respiratory viral infection, we intratracheally infected nine aged (3-yr-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2-infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days postinfection. SARS-CoV-2-infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen concentrations in lung tissue. At 4 days postinfection, oxygen concentrations in lung tissue were significantly lower (mean percentage O, 3.89 ≙ ≈ 27.78 mm Hg) than in the negative control group (mean percentage O, 8.65 ≙ ≈ 61.4 mm Hg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2-infected ferrets.
氧气作为关键元素，对细胞过程有重大影响。感染病原体（如严重急性呼吸综合征冠状病毒2 [SARS-CoV-2]）以及炎症后，组织中可能会出现缺氧状况，从而影响细胞反应。为了开发优化的转化模型，以更好地理解生理和病理生理状态下的氧气状况，确定所产生的氧气浓度是一个先决条件。我们的研究目标是建立一种使用基于发光的微传感器进行氧气测量的侵入性方法，以确定作为SARS-CoV-2研究动物模型的雪貂肺组织中的溶解氧。与人类类似，老年雪貂比幼年动物在感染SARS-CoV-2后更易出现临床症状。为了研究呼吸道病毒感染期间的氧气浓度，我们经气管给9只老年（3岁）雪貂接种SARS-CoV-2。感染SARS-CoV-2的老年雪貂出现了轻度至中度临床症状，并伴有病毒RNA持续脱落，直至感染后14天。感染SARS-CoV-2的雪貂的组织病理学肺损伤评分与肺组织中的氧气浓度显著负相关。在感染后4天，肺组织中的氧气浓度显著低于阴性对照组（平均氧百分比，3.89 ≙ ≈ [27.78毫米汞柱] 低于平均氧百分比，8.65 ≙ ≈ [61.4毫米汞柱]）。总之，我们成功确定了感染SARS-CoV-2的老年雪貂肺组织中的病理生理氧气状况。
