Mechanisms Of Qingluotongbi Granule Intervention On Bone Destruction Of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint swelling, synovial membrane inflammation, and cartilage destruction. Up to date, the etiology of RA is not fully understood. Although there are a few anti-rheumatic drugs showing effectiveness on treating RA, their side effects and toxicity call for new andmore effective natural drugs. So we choice QingLuoTongBi Granule(QLT) which is used by famous doctor very frequently. The present study was therefore designed to investigate the prophylactic and therapeutic effects of QLT on adjuvant arthritis (AA) of rat.And therefore, we studied the intervention of QLT from the inhibition of pathologic histological changes of AA rats,the change of synoviocytes and osteoclast.AIM According to the changes of secondary paw swelling, pain response, polyarthritis,and histological morphological of rat AA, this study tends to clarify prophylactic and therapeutic effects of QLT on rat AA. Meanwhile, Our study aimed to investigat effects of QLT on the ultrastructural changes of synoviocytes, the ultimate effectual cells of pathologic change.To confirm the actions of QLT, this study sought to indentify relationships between the effects of QLT on rat AA and its relative mechanisms by which QLT affected the process of synoviocytes through the expression of RANKL.At the same way,we want to analyse whether QLT had the effect on the expression of RANKL of AA rats, and get to the protective effect on sclerotin destruction through osteoclast by the change of RANKL.METHODS Complete Freund's adjuvant(CFA) was used to induce AA in rats.Prophylactic treatment of intragastric administration with QLT (3.6g,7.2g,14.4g/kg). Tripterygium Glycosides were given as positive control. Continuing administrated QLT to AA rats for 49 days since the 7th day after the AA rat model had been successfully set up to observe sclerotin destroy of each group after the last administration.Fibroblast-like synovocytes were derived from explant culture of tissue fragment of AA rats. Morphological changes of Synovial cells were observed by transmission electron microscope. The proliferation of fibroblast-like synoviocytes was assayed using the MTT assay. IL-1, TNF-a activity of supernants of cultured synoviocytes were examined by thymocyte proliferation assay and radio immuno assay. mRNA expression of RANKL were determined by reverse transcription polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay. Cultivating OC in virto to observe the influence of the ability of TRAP of OC by QLT-contained serum. At the same time,we observe the influence of the proliferation and the resorption pits of OC.RESULTS(1).Prophylactic and therapeutic treatment of rats given 3.6g/kg,7.2g/kg,14.4g/kg QLT suppressed significantly the secondary paw swelling and pain response, as well as down-regulated the index of polyarthritis in AA rats.(2).Given 3.6g/kg,7.2g/kg,14.4g/kg QLT could decrease the proliferation of synoviocytes in AA rats. The supernants of cultured synoviocytes after treatment with QLT suppressed proliferation of fibroblast-like synoviocytes in AA rats.The production of IL-1, TNF-a from synoviocytes were inhibited accordingly by given 3.6g/kg,7.2g/kg,14.4g/kg QLT. QLT decreased mRNA expression of RANKL.(3).OC proliferation effect and the ability of TRAP were obviously inhibited by QLT-contained serum of rats given 3.6g/kg,7.2g/kg,14.4g/kg QLT.And QLT-contained serum of rats given 3.6g/kg,7.2g/kg,14.4g/kg QLT also obviously inhibited the resorption pits of OC.CONCLUSIONS(1)QLT had prophylactic and therapeutic effects on paw swelling, pain, polyarthritic symptoms and articular histopathological changes in rats with AA.(2)QLT had inhibitory effect on reduction the growth of synoviocytes.QLT had inhibitory effect on reduction of IL-1, TNF-a in synoviocytes.QLT decreased mRNA expression of RANKL.(3)QLT-contained serum administrated extraneously could obviously inhibited OC proliferation effect and the ability of TRAP.The resorption pits of OC were also obviously inhibited by QLT-contained serum.So it can protect the decreased bone density which was caused by the OC activation. This protective effect would be related to the inhibiting OC growth and modifying the balance of OB-OC by QLT.