动物造模,药效评价,特应性皮炎 z-bio 2024-08-01 613

　　In 1997, Hiroshi Matsuda from the Faculty of Agriculture at Tokyo A&M University in Japan first reported a mouse model of Nc/Nga that spontaneously produced AD phenotype.

　　Nc/Nga mice are a type of pet mouse in Japan, successfully cultivated by Kyoji Kondo at Nagoya University in 1957. Kondo et al. found that this strain of mice showed changes such as dermatitis, hair loss, anemia, and glomerulonephritis with age, suggesting that it may be an autoimmune disease animal model. In 1997, after re studying this strain of mice, Matsuda et al. identified it as an AD animal model.

　　In 1974, DS hairless type (DS-NH) mice were mutated from the inbred line DS mice. DS-NH mice can spontaneously develop dermatitis under normal living conditions, which is believed to be related to Staphylococcus aureus infection.

　　At 8 weeks, Nc/Nga mice exhibited rough skin, erythema, and scratching behavior in areas such as ears, cheeks, eyelids, nose, and back, leading to erosion, exudation, ulceration, and scab formation. As the age increases, the condition gradually worsens and reaches its peak at 17 weeks. Histological examination showed obvious hyperkeratosis, incomplete keratinization, and thickening of the spinous layer, with an increase in the number of mast cells in the dermis and degranulation of eosinophils. Immunohistochemical analysis showed a high infiltration of CD4+T cells, macrophages, and a small amount of CD8+T cells. The skin barrier function of Nc/Nga mice is disrupted, with increased water loss and decreased levels of ceramides in the skin, which are very similar to human AD.

　　At 9 weeks, DS-NH mice showed obvious scratching behavior, with redness, edema, and erosion on the skin of the face, neck, chest, and forelimb on the flexed side, reaching a peak at 25 weeks. There is infiltration of mast cells, eosinophils, CD4+T lymphocytes, and CD11b+macrophages in the skin lesions. The levels of serum IL-4 and IgE significantly increased.

　　Nc/Nga mice are an ideal animal model for Alzheimer's disease. However, this model has two shortcomings: first, the incidence rate of AD is low. To ensure the appearance of disease phenotypes, sensitive hapten stimulation is usually required; Secondly, it is difficult to quantify the severity of skin lesions. Therefore. This model is widely used in the study of the pathogenesis of AD, but it is limited in clinical drug screening.

　　DS-NH mice are not currently recognized as the best mouse model for studying AD, and their relationship and differences with NC mice and AD still need further exploration.