ABSTRACT
This study is to observe anti-inflammation mechanism of Astragalus heteropolysaccharides (AHPS) on rats with adjuvant arthritis (AA). Rats were treated with AHPS (1 000, 500, and 250 mg x kg(-10, ig) and Tripterygium wilfordii polyglycolide (TWP, 60 mg x kg(-1), ig), separately. TNF-alpha and IL-1beta contents in serum were determined with radioimmunoassay, pathomorphologic changes of synovium of knee joint were observed by histological section with HE staining, synoviocyte apoptosis of knee joint of rats was analyzed by Tunel detection, and Bax and Bcl-2 positive expression were detected by immunohistochemical method. The results were as follows: (1) both AHPS and TWP could improve significantly primary and secondary clinical symptoms of rats with AA and inflammatory response in articular synovium; (2) the contents of TNF-alpha and IL-1beta in serum of rats with AA increased significantly composed with those in groups treated with AHPS (1 000 and 500 mg x kg(-1)), and the amount of synoviocyte apoptosis decreased significantly (P < 0.01 or P < 0.05); (3) the positive expression of Bax in synovium of rats with AA was a little bit higher than that in normal control (P > 0.05), but the positive expression of Bcl-2 significantly increased (P < 0.01). AHPS (1 000 and 500 mg x kg(-1)) could up-regulate positive expression of Bax and down-regulate the positive expression of Bcl-2 significantly (P < 0.05 or P < 0.01). The results show that AHPS can evidently decrease TNF-alpha and IL-1beta level in serum of rats with AA, which is one of molecular mechanisms that AHPS has anti-inflammatory properties. AHPS can induce synoviocyte apoptosis of rats with AA, which is achieved by the regulating effect of AHPS on the positive expression of Bax and Bcl-2.
Subject(s)
Animals , Male , Rats , Apoptosis , Arthritis, Experimental , Drug Therapy , Metabolism , Pathology , Astragalus Plant , Chemistry , Disease Models, Animal , Interleukin-1beta , Blood , Polysaccharides , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats, Wistar , Synovial Fluid , Metabolism , Tumor Necrosis Factor-alpha , Blood , bcl-2-Associated X Protein , MetabolismABSTRACT
Astragalus heteropolysaccharides (AHPS) is obtained from the dried roots of Astragalus membranaceus (Fisch.) Bunge var. mongholious (Bunge) Hsiao. In the present study, we observed its effects on erythrocyte immune adherence function in mice with adjuvant-induced arthritis (AA). The mice were treated intragastrically with AHPS of 1 000, 500, and 250 mg x kg(-1) x d(-1) separately and treated with tripterygium glycosides (TG) of 60 mg x kg(-1) x d(-1) as positive control. The number of complement receptor type 1 (CR1) on erythrocyte, the concentration of circulating immune complex (CIC) in serum and the amount of immune complex (IC) deposition in synovium of knee joint were determined by flow cytometry, polyethylene glycol (PEG-6000) precipitation and ponceau S (P-S) staining and fluorescent immunohistochemistry respectively. The pathological change of knee joint was evaluated by histological section. The results showed that both AHPS and TG improved significantly the primary and secondary local or systemic symptoms of the mice with AA and reduced the synovium hyperplasia, inflammatory cell infiltrate, pannus and cartilage demolish of knee joint, and AHPS of 1 000, 500, and 250 mg x kg(-1) x d(-1) could significantly increase the number of CR1 on erythrocyte, improve the elimination of CIC in the peripheral blood and reduce the deposition of IC in joint synovium in a dose-dependent manner (P < 0.01 or P < 0.05). The results indicate that one of the therapeutic effective mechanisms of AHPS on mice with AA could be to increase gene expression of CR1 of mice with AA.