The Effects And Mechanisms Of Qubi Recipe In Rats Of Collagen-induced Arthritis

Objective:Autoimmune collagen type II-induced arthritis (CIA) rat model to investigate the Qubi side of the treatment of rheumatoid arthritis (RA) and its mechanism, and provide further experimental evidence for Chinese medicine treatment of the diseaseMethods:Selection of SPF male SD rats72, one week after the feeding of the adaptability of randomly selected12as the normal control group, the remaining60of the base of the tail subcutaneous injection of type II collagen and Freund’s complete adjuvant-induced arthritis model.15d after immunization,60of CIA rats were randomly divided into four groups:high dose group of the CIA model group, Tripterygium Glycosides group, Qubi square Qubi side low dose group,15in each group. And begin gavage once daily for four consecutive w. Each group administration as follows:Qubi side high dose group:Dose is6.66g/kg,·d; Dosing concentration for0.666g/ml; Qubi side low-dose group:Dose is3.33g/kg· d,Dosing concentration for0.333g/ml; Tripterygium glycosides:Dose is9.68mg/kg·d, Dosing concentration for0.968g/ml; Delivery volumes are lml/100g weight normal control the size of the group and CIA model rats fed with pure water. The animals were observed arthritis index, joint swelling. Animals were sacrificed after four weeks of treatment, under the light microscope to observe the pathology of the rat ankle injury; ELISA method for the determination of the anti-Ⅱ collagen antibody in animal serum, IL-1, IL-6levels; Determination of serum SOD the two vascular endothelial growth factor (VEGF) receptor FLT-4, MDA and GSH-Px in activity; by immunohistochemical method to detect knee joint synovial tissue and of FLK was1, and hypoxia-inducible factor-la (HIF-la), cytokine changes.All values were expressed as means±standard (x±s) deviation.The difference between the groups regarding the evaluated parameters was tested using the ANOVA test followed by the LSDtest. Results:(1) Joint injury results showed that:compared with normal control group,15d after immunization, rat arthritis index was significantly increased, each model rat arthritis index was no significant difference. Compared with model group, after administration of Tripterygium glycosides group and Qubi of side group rat arthritis index decreased, but not statistically significant. CIA model rats swollen joints was significantly higher than the normal control group; compared with the CIA model group, Tripterygium Glycosides group, high-dose rats Qubi side joint swelling decreased significantly, high dose Qubi side joint swelling degree of the rats was significantly lower than Tripterygium glycosides groupLight microscope visible visible synovial cell hyperplasia, disorganized, and synovial tissue congestion and edema, capillary proliferation, and visible inflammatory cell infiltration; villous proliferation of synovial tissue formation, and can stretch the depths of the joint cavity, or to cartilage surface crawling to the formation of pannus. Under the cover of the pannus cartilage surface can be seen clearly the organization of the cartilage surface degeneration and necrosis. The articular cartilage surface exfoliation, the intra-articular joint cartilage and synovial tissue off the peel.After treatment, proliferation of synovial cells to reduce congestion and edema of the synovial tissue is significantly reduced, reduced the number of vascular proliferation and infiltration of inflammatory cells, pannus formation were significantly reduced. Articular cartilage surface of a small amount of visible flat layer exfoliation, stripping the formation of cartilage, subchondral bone, trabecular bone size, arrangement basically normal. Compared with model group, high dose group of Qubi side and joint damage of Tripterygium glycosides rats significantly reduced; Qubi side high dose group compared with Tripterygium glycosides group, pathological integral decreased significantly.(2) Two were detected by immunohistochemistry in synovial tissue vascular endothelial growth factor (VEGF) receptor FLT-4and of FLK was-1, the results showed that:compared with the normal control group, model group, serum levels of FLK-1, FLT-4levels were significantly increased, high dose group of Tripterygium glycosides group Qubi side serum level of FLK-1is significantly lower than in model group; Qubi side high-dose group, serum FLK-1compared with Tripterygium glycosides group was significantly reduced, Tripterygium Glycosides group and Qubi side high dose group, serum level of FLK-1compared with the model group was significantly lower; Qubi side low dose group, serum FLK-1, of FLT-4levels were significantly decreased, but not statistically significant.Hypoxia-inducible factor-1α (HIF-1α) test results showed that:compared with normal control group, model group, serum levels of HIF-1α levels were significantly increased, while Tripterygium glycosides and Qubi side high-dose group, serum levels of HIF-1α levels than in model group decreased significantly; remove low dose of the paralysis side serum of HIF-1α levels were significantly decreased, but not statistically significant.(3) The serum levels of cytokines measured by ELISA results show that: compared with the normal control group, the CIA model of serum anti-type Ⅱ collagen antibodies, IL-1β, IL-6levels were significantly increased; Tripterygium glycosides group and cured Bi side high-dose group, serum anti-type Ⅱ collagen antibody, IL-1β, IL-6levels are significantly lower than in model group; Qubi side low-dose group, serum anti-type Ⅱ collagen antibody levels in the CIA model group showed no significant difference.Tripterygium glycosides, anti-type Ⅱ collagen antibody Qubi side high dose group, IL-1β levels decreased significantly Qubi side low-dose group, serum IL-1β levels were significantly decreased, while IL-6levels were significantly decreased, but not statistically significant.(4) Of GSH-Px, SOD and MDA activity in the colorimetric assay of serum showed that:compared with normal control group, the CIA model group, serum GSH-Px in the activity of SOD decreased significantly, MDA, activity was significantly increased. Tripterygium glycosides and high and low dose Qubi party can make the serum GSH-Px activity was significantly increased MDA activity decreased significantly, Tripterygium Glycosides and the dose Qubi side also SOD activity was significantly increased.Conclusion: (1) Eradicates paralysis side can significantly reduce the CIA rat ankle joint swelling degree and arthritis index has obvious therapeutic effect on CIA rats, its efficacy is superior to the Tripterygium glycosides.(2) Qubi side can significantly reduce serum anti-type Ⅱ collagen antibody levels, reduce the formation of immune complexes, inhibition of CIA rats with abnormal autoimmune response, and lowered serum IL-1, IL-6, MDA, increase GSH-Px and SOD levels, modulation of immune status to improve synovitis lesions, improving the metabolism of oxygen free radicals, reduce bone destruction, so as to achieve the role of treatment of the CIA.(3) Eradicates paralysis can be lower in synovial tissue vascular endothelial growth factor (VEGF) in the two receptors FLT-4and FLK-1and HIF-1α in content, thus inhibiting angiogenesis and synovial cell proliferation, and improve joint synovitis lesions, treatment of the CIA’s role.