新冠病毒感染 z-bio 2021-02-21 334

　　A group of researchers from the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, will use organ chip technology to simulate lung tissue with a group of researchers from the Kunming Institute of Zoology, Chinese Academy of Sciences, and establish an in vitro microphysiological system. Lung damage and immune response caused by new coronavirus infection. Human research on the pathogenic mechanism of new coronavirus and rapid drug evaluation is a new strategy and new technology.

　　 The new coronavirus (SARS-CoV-2) infection has caused a pandemic, and the number of confirmed cases of new coronary pneumonia is still increasing, posing a serious threat to human health. The lung is the main target organ for SARS-CoV-2 infection. The clinical symptoms of new-onset coronary atherosclerosis vary according to the severity, mainly fever, general malaise and dry cough. Severely ill patients involve multiple organs and may also lead to multiple organ failure. Studies have shown that the "inflammatory factor storm" caused by the overreaction of the human immune system is one of the main reasons why patients change from mild to severe. Currently, most new clinical treatments for coronary pneumonia are based on comprehensive treatment, but some drugs are still in short supply. Cell and animal models have long been used in the study of the new coronavirus, but they still have some limitations. At this stage, there is still a lack of research models that can reflect human response to new coronavirus infections at the level of tissues and organs. This is also one of the bottlenecks that severely limits the current development of new coronavirus drugs. Organ chip is a new, latest cross-scientific technology that combines physics, chemistry, engineering, biology and other interdisciplinary methods, which can bring a variety of human tissues and organs into one of a few fluid controls. This kind of chip can be used to build. The size is square centimeters. The model is used to reflect the key structure and biological functions of human organs. In particular, the human body's response to various external factors can be reproduced in an unprecedented way, and it may be widely used in life science research, disease research, new drug development, etc. Alveoli are the basic functional unit of the human lung, and the capillary barrier of the alveoli is essential for maintaining gas exchange in the lung and resisting external pathogen infection. In this study, the researchers first used organ chip technology to construct human alveolar functional units from a biological point of view, and then conducted a new coronavirus infection experiment. Researchers have started with the complex structure and functional characteristics of human lung tissue, and simulated the microenvironment of human alveolar tissue in perfusible microchips with a multi-chamber design. In the experiment, multiple human alveolar epithelial cells, pulmonary microvascular endothelial cells and human peripheral blood immune cells were dynamically co-cultured in the microenvironment (alveolar side/vascular side) of the chip porous membrane. Including human-derived cells, mechanical fluids, tissue interfaces, etc. Complex factors have been established to conduct new coronavirus infection experiments on the chip. The results show that when the epithelial cells on the alveolar side of the chip are exposed to the new coronavirus, a large amount of virus replication will be seen in the epithelial cells, thereby destroying the integrity of the lung tissue barrier. Transcriptome analysis showed that SARS-CoV-2 infection caused different response mechanisms in the two cells, respectively activating the type I interferon pathway in epithelial cells and the JAK-STAT pathway in endothelial cells. According to the calculation of viral load, human alveolar epithelial cells are highly sensitive to the virus and are the main site of virus replication, but the viral load of human lung microvascular endothelial cells is low, and the endothelium is indirectly infected by the virus. Cells suggest that they may affect cells. In addition, viral infection may increase the attachment of human peripheral blood immune cells to vascular endothelial cells on the chip side and release many inflammatory factors (IL-1β, IL-6, etc.). , IL-8, TNF-α)), suggesting that a new coronavirus infection in lung tissue may activate human immune cells to release a variety of inflammatory factors and induce damage to pulmonary microvascular endothelial cells. Using this model, the researchers also conducted a preliminary study and evaluation of the efficacy of antiviral compounds.

　　 This research uses organ chip technology to establish a human new coronary pneumonia disease model at the tissue level. It mimics the lung barrier dysfunction, immune cell adhesion, inflammatory factor release and lung endothelial cell damage caused by new coronavirus infection in vitro. A series of important pathophysiological processes reflect the pathogen-host interaction mediated by multicellular complex factors in the new coronavirus infection. The model system has the characteristics of short modeling cycle, low cost, human source, easy monitoring, etc., can obtain dynamic biological information that is difficult to obtain by conventional methods, and can be extended to study the mechanism of new organ coronary heart disease.