动物造模,类风湿关节炎,药效评价 zi-bio 2024-10-31 722

　　Objective: To explore the effects of all trans retinoic acid (ATRA) on the joint tissue structure, serum expression levels of inflammatory cytokines, and expression levels of cartilage injury related proteins during the formation phase of type II collagen (CIA) induced rheumatoid arthritis in rats.

　　Method: Female Wistar rats aged 6-8 weeks were randomly divided into a blank control group, a solvent control group, and ATRA dose groups. The solvent control group and ATRA dose groups were given tail intradermal injection of C Ⅱ and incomplete Freund's adjuvant to induce rheumatoid arthritis. The blank control group rats were given an equal amount of physiological saline in the same way. Starting from the second day of initial immunization, rats in each dose group of ATRA were intraperitoneally injected with different doses (0.05, 0.5, 5 mg/kg) of ATRA oil. The solvent control group was intraperitoneally injected with an equal volume of corn oil, while the blank control group was intraperitoneally injected with an equal volume of physiological saline, three times a week, for three consecutive weeks. Observe the effects of ATRA on arthritis index (AI) score, pathological morphology of knee and ankle joint tissue, expression levels of related inflammatory cytokines in serum, and expression levels of cartilage injury related proteins in rats.

　　Result: Since the 15th day of initial immunization, the AI values of all dose groups of ATRA and solvent control group were significantly higher than those of the blank control group (P<0.05). The AI values of the solvent control group tended to stabilize, while the AI values of all dose groups of ATRA showed an upward trend and were lower than those of the solvent control group (P<0.05); Pathological sections of the knee and ankle joints can be seen, and the effect of atra on various dosage groups and solvents is p=">0.05"; In addition, compared with the solvent control group, the ATRA dose groups of interleukin-17A (IL-17A) and tumor necrosis factor- α (TNF)- α） Decreased secretion (P<0.05), increased secretion of interleukin-10 (IL-10) (P<0.05); The expression of whole chain metalloproteinase-4 (ADAMTS-4) and matrix metalloproteinase-3 (MMP-3) in the knee joint was downregulated (P<0.05), while="" there="" was="" no="" statistically="" significant="" difference="" in="" the="" expression="" of="" other="" cartilage="" injury="" related="" proteins="" p="">0.05).

　　Conclusion: During the formation phase of collagen induced arthritis, ATRA can inhibit TNF- α、 The secretion of pro-inflammatory factors such as IL-17A promotes the secretion of IL-10, thereby reducing the inflammatory response during the formation phase of arthritis in CIA rats. ATRA can delay the progression of arthritis during its formation phase, and its mechanism of action may be related to correcting Th1/Th2 and Th17/Treg imbalances.