动物造模,新冠病毒 z-bio 2022-02-06 277

　　The new coronavirus (SARS-CoV-2) infection has caused a global pandemic, posing a major public health crisis, and seriously threatening human health. It has been clinically found that patients with new coronavirus infection mainly have respiratory symptoms, but 20%-50% of patients still have obvious gastrointestinal symptoms, including abdominal pain, diarrhea, blood in the stool, and even intestinal perforation. It is also reported that viral RNA can be found in the stool samples of COVID-19 patients, suggesting that the intestine may be another major target organ attacked by the new coronavirus. Although there are cellular and animal-based infection models, there are not many studies on the intestinal infection induced by the new coronavirus, and the mechanism of infection is still unclear. In particular, the existing research models still have certain limitations, and it is still difficult to reflect the organ-specific key characteristics of the human intestinal tissue interface, multicellular composition, and mucus secretion.

　　 The intestine in the human body has the functions of digestion, absorption and secretion, and it is also the body's largest immune organ. The intestinal tissue contains complex multicellular components, intestinal villi structure, mucosa and microbial flora, among which the intestinal epithelial tissue barrier is essential to maintain the host-microbe homeostasis and resist external pathogen infections. In this work, starting from the structure and functional characteristics of the human intestine, a multi-layer design perfusion intestinal chip device was established biomimically to simulate the intestine containing a variety of complex factors such as human intestinal cells, tissue interfaces, 3D cell matrix and mechanical fluid. Organizational microenvironment. In the experiment, the researchers performed 3D dynamic co-culture of human intestinal epithelial cells, mucus secreting cells, human umbilical vein endothelial cells, and human immune cells in the upper and lower chambers of the multilayer intestinal chip device to form a human intestinal epithelium-blood vessels The endothelial interface features the intestinal tissue barrier, and presents typical intestinal villi structure, mucus secretion and barrier integrity functions.

　　Using this chip device, researchers conducted research on new coronavirus infection in the BSL-3 laboratory of the Kunming Institute of Zoology, Chinese Academy of Sciences. When the intestinal chip device is exposed to the new coronavirus, a large number of viral replications can be seen in human intestinal epithelial cells, and at the same time, villi are destroyed, mucus secreting cells are abnormally distributed, and the expression of cadherin is reduced. In addition, virus infection can also cause damage to vascular endothelial cells, a significant decrease in the number of cells, and a decrease in the expression of intercellular junction protein (VE-cadherin). Transcriptome analysis found that viral infection can induce abnormal responses in human intestinal epithelial cells and vascular endothelial cells, including activation of immune response-related signal pathways (such as TNF and NF-kappa B), pro-inflammatory cytokines and chemokine-related genes (such as TNF, IL-6 and CXCL10) increased expression and a series of changes.

　　In this work, the researchers first tried to use the microfluidic bionic intestinal chip device to explore the intestinal infection induced by the new coronavirus, and found that the new coronavirus can cause a series of pathological processes such as human intestinal tissue barrier dysfunction, endothelial cell damage and inflammation. This intestinal chip infection model can reflect the physiological characteristics of intestinal organs based on the tissue level and the pathological response to the new coronavirus to a certain extent, and has the advantages of short modeling cycle, low cost and easy dynamic observation. The follow-up work can further combine the human body's various intestinal immune cells and intestinal microbes to establish a more complex intestinal immune microenvironment on the chip, which is important for the in-depth study of the interaction between intestinal pathogens and the host and the route of virus transmission. significance.