Preliminary Study On The Angiogenesis Mechanism Of Mongolian Medicine Compound Sendeng-4 Against Rheumatoid Arthritis By Tc-99m-3prgd(2) Imaging

181 Objectives: To observe the uptake of 99mTc-3PRGD2 in rat models of rheumatoid arthritis (RA) before and after treatment with Mongolian medicine, in order to explore it`s therapeutic mechanism for RA, and provide theoretical foundation clinically. So as to establish an evaluation model to screen and verify the efficacy of Mongolian medicine in vivo.\n Methods: The healthy female SD rats were randomly divided into collagen-induced arthritis (CIA) group (n=176) and blank control group (n=24). Bovine collagen type II emulsion was used for arthritis induction to establish CIA models. Then the rats successfully modeled in the CIA group were randomly divided into Mongolian medicine (compound Senden-4) treatment group (n=24), TNF-α Antagonist (etanercept) treatment group (n=24) and untreated group (n=24). SPECT/CT imaging was performed before and after model established and 6 weeks after treatment. The mediastinum was select as non-target (NT) area and the target (T)/NT ratios were calculated. The serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and ανβ3 in each rats group before and after treatment were measured. Pathological and immunohistochemical detection were performed. Statistical methods such as one-way analysis of variance, Dunnett9s T3 method, Pearson and Spearman correlation analysis were used to analyze the data. (α = 0.05)\n Results: 1.There were 94 CIA models successfully established, the model success rate was about 58%, in which the clinical manifestations of the rats were significant. The pathological score injury index and the expression levels of VEGF, TNF-α, αVβ3, CD31, and CD34 in the synovial tissue were significantly different from those in the blank control group (P 0.05). After successful modeling, the difference between the two groups was statistically significant (P \u003c0.05). 4. The T/NT value of the diseased joints in the CIA group after modeling was positively correlated with its arthritic index, serum VEGF, TNF-α, αVβ3 level, pathological score injury index and VEGF, TNF-α, αVβ3, CD31, CD34 expression levels in synovial tissues (r=0.562,0.721,0.521,0.391,0.606,0.408,0.561,0.594,0.669,0.365,P\u003c0.05). 5. In the CIA group, the T/NT values of rats treated with etanercept and Senden-4 decreased. The T/NT values before treatment were 0.543 ± 0.223, 0.509 ± 0.140, and 0.262 ± 0.868, 0.223 ± 0.529 after treatment, respectively, and the differences were statistically significant (P \u003c0.05). With the treatment of the two drugs, synovial neovascularization decreased, arthritis index scores and the levels of VEGF, TNF-α, αVβ3 in serum and the expression levels of VEGF, TNF-α, αVβ3, CD31, and CD34 in synovial tissues were decreased. The T/NT values of the two drug treatment groups were positively correlated with the above indicators. (Etanercept treatment group r=0.485,0.624,0.607,0.598,0.609,0.549,0.479,0.496,0.706,P\u003c0.05; Senden-4 treatment group r=0.662,0.659,0.789,0.807,0.483,0.570,0.553,0.483,0.577,P\u003c0.05).\n Conclusions: 1. Mongolian medicine compound Sendeng-4 can control the progression of rheumatoid arthritis by inhibiting angiogenesis. 2. 99mTc-3PRGD2 targeted receptor imaging has clinical application value in verifying Mongolian medicine treatment mechanism and treatment effect.