Study On The Role Of Glutamate Signal And Its Mechanism In Rheumatoid Arthritis

Objective:Establish the rat Collagen-induced arthritis (CIA) model, taking the ionic glutamate receptors as the research target, applying the receptor antagonist MK-801 and NBQX Respectively to observe the effects of different receptor antagonists on behavior of rats, to observe the downregulation and upregulation of COX-2, JAK3 in serum and tissue fluid after using the antagonist. Test serum glutamate level in RA patients to analyze and infer the concentration of glutamic acid in the blood rising whether can be used as the independent risk factors of early bone destruction in RA, thereby, to study the role of glutamatergic related signaling pathway in rheumatoid arthritis.Methods:Using Wistar rats as the experimental object, the rats were randomly divided into 6 groups,6 rats in each group. The first group:blank control group; The second group:CIA group; The third group:CIA+MK-801 group; The fourth group:CIA+NBQX group; The fifth group: CIA+MK-801+NBQX group; The sixth group:8.7%DMSO+CIA group. Observe and study the behavior changes of CIA rats after injecting different antagonists. Behavior evaluation contents include tenderness situation——using mechanical paw withdrawal threshold to evaluate the change of swelling conditions. Use drainage method to measure the foot volume to represent the swelling situation. Then collect the blood from the heart of rats and get the tissue homogenate, to test the downregulation and upregulation of COX-2, JAK3 in serum and tissue fluid after using the antagonist. At the same time, Collecting blood samples from rheumatoid arthritis patients and healthy human, testing the concentration of glutamic acid in blood of rheumatoid arthritis patients and healthy human respectively, Analyses and evaluate the relationship between the anti CCP antibody, ESR and X-ray, B ultrasound etc.Results:After the CIA rats were injected with different glutamate receptor antagonists, using MK-801, NBQX alone or using the combination of these two antagonists, these two methods all can show good recovery mechanical paw withdrawal threshold (PWT) that the analgesic effect, and the analgesic effect lasts more than 24h, about the analgesic effect, NBQX better than MK-801. But whether alone or combined use of these two antagonists, can not change CIA big rat foot metatarsus swelling. NMDA receptor antagonist MK-801 can decrease the expression of cox-2. But either alone or combination of the two antagonists cannot affect the increased expression of Jak3 caused by the CIA.There is a significant difference between the patients with rheumatoid arthritis and normal human glutamic acid concentration (P<0.01).Serum glutamate concentration in patients with RA, was negatively correlated with B ultrasound grading(P<0.01).Conclusion:Glutamate receptor antagonists MK-801 and NBQX could reduce the pain well. NBQX much better than MK-801, But on the swelling are invalid. NMDA receptor and cox-2 inflammatory pathways have certain interactions. But for Jak3,it can not be found cross function with glutamate signaling pathways by this experiment.The concentration of glutamic acid and bone erosion has certain relation, can be used as a marker for early diagnosis of RA, which has the value of clinical application and scientific research in detection of patients with rheumatoid arthritis.