动物造模,药效评价,关节炎 z-bio 2024-08-27 414

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

　　(1) The replication method involves high-pressure sterilization of liquid paraffin, followed by inactivation of BCG at 80 ° C for 1 hour. BCG is added to the liquid paraffin to prepare a 10g/L emulsion, which is thoroughly ground and mixed to obtain CFA. CFA 0.1ml is injected intradermally into the left hind paw of rats to induce inflammation.

　　(2) The primary lesion of the model is mainly characterized by early inflammatory response in the inflamed area. After 18 hours of inflammation, the swelling of the left foot reaches its peak and gradually decreases after 3 days. After 8 days, it swells again. Secondary lesions generally appear around 10 days after inflammation, manifested as swelling of the contralateral and forefoot, progressively worsening, difficulty in movement, joint nodules in the ears and tail, allergic keratitis, and weight loss, which are similar to human RA. Measure the significant swelling of the feet with a foot claw meter. MRI examination of local pathological changes in the joints of AA rats revealed two distinct stages of secondary contralateral paw development during the course of the disease. The first stage occurs 10-18 days after inflammation, characterized by synovitis, synovial cellulose deposition, and joint cyst swelling around the joints; The second stage is between 18-30 days, characterized by persistent soft tissue inflammation, accompanied by osteolytic periostitis, periosteal new bone formation, monocyte infiltration, vascular opacities, and complete joint adhesion. The changes discovered through MRI are consistent with the course of biochemistry, cytology, and histology.

　　Rat AA is a chronic systemic immune inflammation characterized by multiple arthritis and mediated by T cells. Manifesting as low Ts cell function and T cell mitogen response, its immunological indicators are slightly different from CIA. The protein levels in the serum of AA rats showed parallel changes with inflammatory parameters such as joint swelling and IL-6 activity. The levels of binding globulin, mucin, a2 microglobulin, secreted protein factor-3, alpha antitrypsin, C-reactive protein, etc. in the serum increased, while the levels of kininase binding protein, alpha inhibitory factor III, apolipoprotein A-I, apolipoprotein A-IV, ovalbumin, transferrin, etc. decreased. In the pathogenesis of rheumatoid arthritis, steroids, sex hormones, and other mediators secreted by the endocrine system, as well as norepinephrine or substance P secreted by the peripheral nervous system, reach synovial cells and specifically bind to corresponding receptors, regulating the local inflammatory process through the feedback system. The sympathetic nervous system secretes norepinephrine, adrenaline, endorphins, and methionine enkephalin (Met En), which can promote the secretion of IL-6 and IL-8 in synovial fibroblasts of RA patients.

　　(3) Rheumatoid arthritis in comparative medicine is a chronic, inflammatory, and systemic autoimmune disease. The basic pathological changes are synovitis, acute phase synovial swelling and exudation, neutrophil infiltration, chronic phase synovial hyperplasia and thickening, forming vascular opacities, which are the pathological basis for joint destruction, joint deformity, functional impairment, and irreversible disease progression. Inflammation and exudation of synovium, as well as 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 many animals, such as rats, mice, rabbits, sheep, etc., but its incidence rate, onset time and arthritis symptoms are different. Even the incidence of the disease is different between rats and mice. Rat or mouse rheumatoid arthritis animal models share many similarities with human rheumatoid arthritis, but currently there is no model that can fully simulate the condition of human rheumatoid arthritis. Such as the onset of the disease, the severity of arthritis, the ways in which it affects the joints, 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, commonly used methods for replicating animal models of adjuvant arthritis include: ① Tetramethylpentadecane induced arthritis (PIA), which is a serum positive experimental arthritis characterized by humoral and cellular immune abnormalities, mediated by CD4+T cells. This inducer amplifies polyclonal T cells, further causing lymph node lesions and synovial infiltration. ② Adjuvant carrageenan induced arthritis (ACII), sensitive mice were selected. CFA was first injected subcutaneously, and carrageenan was injected subcutaneously at different times in the plantar area. After injection, swelling was observed in the feet and ankle joints of DBA/1 mice, which became more pronounced after 3 weeks of injection. Pathological observation shows subcutaneous congestion, lymphocyte infiltration, and granuloma formation. This model is mainly used for screening inflammatory drugs and other research Protein polysaccharide induced arthritis, in which human embryonic cartilage protein is added to complete or incomplete Freund's adjuvant, and susceptible strains (such as RALB/c) are injected intraperitoneally in three doses, can lead to the occurrence of chronic arthritis after 4 weeks. Female mice are more susceptible than males, and the development of arthritis, the presence of rheumatoid factors, and the deposition of immune complexes show that this model has some similar characteristics to rheumatoid arthritis Streptococcus induced arthritis can be induced by intraperitoneal injection of a cell wall peptidoglycan polysaccharide suspension from group A streptococcus or several other bacteria into susceptible strains of rats such as LEWS rats, which can induce severe erosive arthritis.