动物模型,关节炎 z-bo 2020-08-10 507

　　Since the first animal model of collagen-induced arthritis was established in the 1970s, studies have confirmed that there are anti-collagen antibodies in the serum and synovial fluid of patients with rheumatoid arthritis, and this autoimmune response to collagen tissue can explain the class Rheumatoid arthritis has the characteristics of systemic and chronic continuous development.

　　(1) Replication method: Dissolve type Ⅱ collagen (a protein isolated from the immune system and present in articular cartilage in large quantities) in 0.1 mol/L of acetic acid, stir and fully dissolve it at 4°C, with a concentration of 2 g/L Place the inactivated BCG vaccine (BCG) in liquid paraffin to prepare 2g/L complete Freund's adjuvant, put it in a refrigerator at 4°C overnight, and mix and emulsify the two in equal volume to prepare type II collagen emulsion. This emulsion was injected intracutaneously with 0.1 ml of the emulsion into the tail base of the mouse to cause inflammation, and 0.1 ml of the emulsion was injected intraperitoneally on the 21st day as a challenge injection.

　　(2) Model characteristics After the first immunization injection, multiple small ulcers can be formed at the intradermal injection site. This is a local inflammatory stimulus. Generally, the scabs can heal on their own in about 1 week; arthritis signs: 24 days after inflammation, mice Joint swelling occurred, first two hind feet, then spread to the forefoot and tail, and gradually worsened, reaching a peak at 36 days. The paw changes were measured with a paw instrument, and inflammation was caused for 28 days. The paws were significantly larger than the normal control group. During the course of the disease, the animal's coat loses its luster, slightly loses hair, loses weight, and is accompanied by inflammatory lesions in the ears and tail. Single or multiple joints are red and swollen, and animals are inconvenient to move. Under light microscope, early synovial tissue has infiltration of neutrophils, monocytes, and lymphocytes, followed by synovial cell proliferation, disordered arrangement, and cellulose infiltration Collagen fiber deposition, fibrinoid necrosis, that is, synovitis; under the electron microscope, synovial cell mitochondria decreased, lysosomes increased, and intercellular space increased; the bacterial culture of the exudate in the joint cavity was negative, indicating that the CIA is not Infectious inflammation.

　　The bone destruction of CIA is closely related to the abnormal expression of osteoclasts. Using tissue morphology to determine the bone loss of the proximal tibia and lumbar spine of CIA mice, it was found that there were a large number of osteoclasts and temporary bone formation in the early stage, which caused inflammation. At 4 weeks, the number of osteoclasts and bone trabeculae in the proximal tibia was close to the joint inflammation area by 4 times compared with the control group. The lumbar spine showed no symptoms of arthritis, and the recruitment of osteoclasts was later. As time progressed, The proximal tibia and lumbar spine have bone resorption.

　　(3) Comparative Medicine CIA, as an animal experimental model of RA, is manifested as multiple peripheral arthritis, local joint swelling and severe joint deformity. The pathological changes are proliferative synovitis, destruction of articular cartilage, bone erosion, and inflammatory cell infiltration in the joint cavity. High titers of IgG antibodies against self-type II collagen can be detected in the body. These clinical manifestations and laboratory indicators are closely related to human RA and are an ideal model for screening and researching drugs for treatment of RA.

　　Different strains of mice are genetically susceptible to CIA. B10RⅢ and RⅢs/J mice have a common major histocompatibility complex on chromosome 17, which is of great significance to CIA. In addition, it was also found that the main site controlling CIA (Mcial; Lod 4.12) is located on chromosome 3, and is in the same region as the main site controlling experimental allergic encephalomyelitis (EAE); it is also identified on chromosome 13 A site that controls CIA indicates that there is a new site that controls CIA outside the MHC region, and that CIA is controlled by multiple genes. BB rats are susceptible to CIA, and there are susceptibility genes on their MHC alleles.