动物模型,关节炎 z-bo 2020-08-10 576

　　Adjuvant arthritis (AA), also known as Freund's adjuvant arthritis, was founded by bacteriologist Freund in the 1950s, which is the basic method of immune arthritis animal model.

　　(1) Method of replication: Autoclave liquid paraffin, inactivate BCG at 80°C for 1 hour, add BCG to liquid paraffin to prepare a 10g/L emulsion, fully mill and mix, and then get CFA. Inflammation caused by intradermal injection of CFA 0.1ml.

　　(2) Model characteristics The primary lesions mainly manifested as the inflammatory reaction at the early inflamed site. 18 hours after the inflammation, the left foot swelled to the peak value, and continued for 3 days and then gradually reduced, and then swelled again after 8 days. The secondary lesions generally appeared after the inflammation. About 10 days later, it showed swelling of the contralateral side and forefoot with progressive increase, inconvenient mobility, arthritis nodules in the ears and tail, allergic keratitis, and weight loss. These manifestations are similar to human RA. The feet are obviously swollen when measured with a foot device. MRI detected local pathological changes in the joints of AA rats, and found that the secondary contralateral foot had two distinct stages in the course of the disease. The first stage occurs 10 to 18 days after inflammation, and inflammation around the joint is characterized by synovitis, synovial fibrosis, and joint cyst swelling; the second stage is 18 to 30 days, manifested as persistent soft tissue inflammation, accompanied by Osteolytic periostitis, new bone formation in the periosteum, monocyte infiltration, pannus formation, and complete joint adhesion. The changes found by MRI are consistent with the course of biochemistry, cytology, and histology.

　　rat AA is a chronic systemic immune inflammation mediated by T cells and characterized by polyarthritis. It is manifested by low Ts cell function and low T cell mitogen response, and its immunological indicators are slightly different from CIA. The protein level in serum of AA rats changed in parallel with inflammatory parameters (joint swelling, IL-6 activity, etc.). Serum haptoglobin, mucin, a2-microglobulin, secreted protein factor-3, a-antitrypsin, C-reactive protein, etc. are all elevated, while kallikrein binding protein, a inhibitory factor III, Apolipoprotein A-I, apolipoprotein A-IV, ovalbumin, transferrin, etc. decreased. In the onset of rheumatoid arthritis, steroid hormones, sex hormones, etc. secreted by the endocrine system and mediators such as norepinephrine or substance P secreted by the peripheral nervous system reach the synovial cells and specifically bind to the corresponding receptors, which are regulated by the feedback system Local inflammation process. Norepinephrine, epinephrine, endorphins and methionine enkephalin (Met-Enk) secreted by the sympathetic nervous system can promote the secretion of IL-6 and IL-8 in synovial fibroblasts of RA patients.

　　(3) Comparative Medicine Rheumatoid arthritis is a chronic, inflammatory, and systemic autoimmune disease. The basic pathological changes are synovitis, synovial swelling and exudation in the acute stage, neutrophil infiltration, hyperplasia and hypertrophy of the synovial membrane in the chronic stage, forming pannus, which causes joint destruction, joint deformity, dysfunction, and disease The pathological basis of entering the irreversible stage. Inflammation and exudation of the synovial membrane, fibrosis and degeneration of cartilage are the main processes leading to joint swelling, stiffness and deformation in human rheumatoid arthritis patients.

　　Freund's adjuvant can immunize a variety of animals, such as rats, mice, rabbits, sheep, etc., but the incidence, time of onset, and symptoms of arthritis are different. Even the incidence is different between rats and mice. Both rat or mouse rheumatoid arthritis animal models have many similarities with human rheumatoid arthritis, but there is no model that can fully simulate human rheumatoid arthritis. Such as the beginning of the disease, the degree of arthritis, the way the joints are affected, and various additional clinical and systemic manifestations. Different animal models can provide unique research content for the etiology and pathology of rheumatoid arthritis. In addition, the commonly used methods for replicating adjuvant arthritis animal models include: ①Tetramethylpentadecane-induced arthritis (PIA) is a seropositive experimental arthritis characterized by abnormal humoral and cellular immunity It is mediated by CD4+ T cells. The inducer expands polyclonal T cells, which further causes lymph node disease and infiltrates the lubricating membrane. ②Adjuvant carrageenan-induced arthritis (ACⅡ), select sensitive mice, first inject CFA subcutaneously, and inject carrageenan subcutaneously at different times. After injection, DBA/1 mice showed swelling of the feet and ankle joints, which was more obvious after 3 weeks of injection. Pathological observation showed subcutaneous congestion, lymphocyte infiltration and granuloma formation. This model is mainly used for research such as the screening of inflammatory drugs. ③Proteoglycan-induced arthritis, human embryo cartilage protein added to complete or incomplete Freund’s adjuvant, intraperitoneal injection of susceptible strains (such as RALB/c) in 3 times, can cause chronic polyarthritis after 4 weeks Female mice are more susceptible than males. The development of polyarthritis, the presence of rheumatoid factors, and the deposition of immune complexes show that this model has some characteristics similar to rheumatoid arthritis. ④Streptococcal-induced arthritis, cell wall peptidoglycan-polysaccharide suspension from group A streptococcus or several other bacteria alone, intraperitoneal injection of susceptible strains of rats such as LEWS rats can induce severe erosive joints inflammation.