Study Of The Regulatory Effects Of Total Flavonoids Of Astragalus On OPG/RANKL/NF-κB Pathway In Rats With Adjuwant Arthritis

The model of adjuvant arthritis in rats was established by Freund’s complete adjuvant and the anti-inflammatory effect and mechanism of total flavonoids of Astragalus (TFA) on adjuvant arthritis were studied.The 42 rats were randomly divided into 6 groups:the control group, model group, positive group (MTX 3 mg/kg) and the total flavonoids of Astragalus high, med and low dose group (TFA 100 mg/kg, 50 mg/kg,25 mg/kg). Excepting for the control group, the rats were intradermally injected Freund’s complete adjuvant 0.1 ml of 10 mg/ml BCG concentration and established adjuvant arthritis model. The next day, every group was intragastrically administrated corresponding drugs for 29 days. The body weight and primary swelling were measured every 4 days, after 16 days the arthritis indices were observed every 2 days. On 28 day, the heart blood was collected and the serum was separated, then the contents of IL-1β,TNF-α, PGE2, OPG and RANKL in serum were determined by ELISA method. The thymus and spleen indices were measured, the ankle joint histopathological changes of synovial tissue and histological scores in ankle joints were observed by HE staining. Immunohistochemical method was used to observe the expression of NF-κB p65 in synovial membrane and chondrocytes of rats.An investigation shows that TFA could reduce primary swelling and multiple arthritis index, reduce spleen index and thymus index, and increase the weight of adjuvant arthritis rats.The concentrations of the serum IL-1, TNF-a, PGE2, RANKL increased significantly and concentration of the OPG decreased obviously in the model group by ELISA. TFA could inhibit the secretion of IL-1β, TNF-a, PGE2, RANKL, and promote the secretion of the OPG and OPG/RANKL in sera. TFA could reduce obviously the infiltration of inflammation cell, synovial hyperplasia and the vascular proliferation in AA rats by HE staining. The expression of NF-κB p65 in synovial cells of the model group, TFA could inhibit the expression of NF-κB p65 by Immunohistochemistry.The study show that the TFA can reduce significantly the degree of ankle primary swelling, multiple arthritis index, immune organ index and increase the body weight of AA rats.On other hand, the TFA can recover the articular abnormal morphology of the AA rats, reduce synovial NF-κB p65 expression of the AA rats, inhibit the secretion of IL-1β,TNF-α, PGE2, RANKL, and promote the secretion of the OPG and OPG/RANKL in serum. The change may be the primary mechanisms of TFA in the treatment of AA.