Chepur S V, Alekseeva I I, Vladimirova O O, Myasnikov V A, Tyunin M A, Ilinskii N S, Nikishin A S, Shevchenko V A, Smirnova A V
FSBI «State Research Testing Institute of Military Medicine» of the Ministry of Defense of the Russian Federation.
Vopr Virusol. 2022 Jan 8;66(6):442-451. doi: 10.36233/0507-4088-63.
Verification of histological changes in respiratory system using Syrian (golden) hamsters (Mesocricetus auratus) as experimental model is an important task for preclinical studies of drugs intended for prevention and treatment of the novel coronavirus infection COVID-19.The aim of this work was to study pathological changes of pulmonary tissue in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) experimental infection in Syrian hamsters.
Male Syrian hamsters weighting 80-100 g were infected by intranasal administration of culture SARS-CoV-2 at dose 4 × 104 TCID50/ml (TCID is tissue culture infectious dose). Animals were euthanatized on 3, 7 and 14 days after infection, with gravimetric registration. The viral load in lungs was measured using the polymerase chain reaction (PCR). Right lung and trachea tissues were stained with hematoxylin-eosin and according to Mallory.
The highest viral replicative activity in lungs was determined 3 days after the infection. After 7 days, on a background of the decrease of the viral load in lungs, a pathologically significant increase of the organ's gravimetric parameters was observed. Within 3 to 14 days post-infection, the lung histologic pattern had been showing the development of inflammation with a succession of infiltrative-proliferative, edematousmacrophagal and fibroblastic changes. It was found that initial changes in respiratory epithelium can proceed without paranecrotic interstitial inflammation, while in the formation of multiple lung parenchyma lesions, damage to the epithelium of bronchioles and acinar ducts can be secondary. The appearance of epithelioid large-cell metaplastic epithelium, forming pseudoacinar structures, was noted as a pathomorphological feature specific to SARS-CoV-2 infection in Syrian hamsters.
As a result of the study, the specific features of the pathology of the respiratory system in SARSCoV-2 infected Syrian hamsters were described. These findings are of practical importance as reference data that can be used for preclinical studies to assess the effectiveness of vaccines and potential drugs.
以叙利亚(金黄)仓鼠(Mesocricetus auratus)作为实验模型,验证呼吸系统的组织学变化,对于旨在预防和治疗新型冠状病毒感染COVID-19的药物临床前研究而言是一项重要任务。这项工作的目的是研究叙利亚仓鼠感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2,属于冠状病毒科:冠状病毒亚科:β冠状病毒;Sarbecovirus)后肺组织的病理变化。
体重80 - 100克的雄性叙利亚仓鼠通过鼻内给予剂量为4×104 TCID50/ml的SARS-CoV-2培养物进行感染(TCID为组织培养感染剂量)。在感染后第3、7和14天对动物实施安乐死,并进行重量记录。使用聚合酶链反应(PCR)测量肺中的病毒载量。右肺和气管组织用苏木精 - 伊红染色并按马洛里染色法染色。
感染后3天确定肺中病毒复制活性最高。7天后,在肺中病毒载量下降的背景下,观察到器官重量参数出现具有病理意义的增加。在感染后3至14天内,肺组织学模式显示炎症发展,伴有一系列浸润 - 增殖、水肿 - 巨噬细胞和纤维化变化。发现呼吸上皮的初始变化可以在无旁坏死性间质炎症的情况下发生,而在多个肺实质病变形成过程中,细支气管和腺泡导管上皮的损伤可能是继发性的。出现形成假腺泡结构的上皮样大细胞化生上皮,被视为叙利亚仓鼠感染SARS-CoV-2的特异性病理形态学特征。
作为研究结果,描述了感染SARS-CoV-2的叙利亚仓鼠呼吸系统病理学的具体特征。这些发现作为参考数据具有实际重要性,可用于临床前研究以评估疫苗和潜在药物的有效性。