Paralysis More Soup Experimental Study, The Therapeutic Mechanism Of Rheumatoid Arthritis Bone Erosion

Background:Rheumatoid arthritis (RA), is a chronic systemic autoimmunedisease. Its prevalence in adults in China is about 0．32%-0．36%, which is lower thanthat in other places 1% . And it is one of major diseases causing disability in ournation.The major pathological change of RA is synovialis hyperplasia andinflammation, inflammatory cell infiltration, formation of pannus and the erosion ofcartilage and bones. which lead to the destruction of bone and functionalincapacitation of joints.Recently, the mechanism of cartilage and bone destruction in RA has become aresearch point at issue. The primary procedure of cartilage and bone destruction ismatrix degradation. MMP and TIMP play an important role in this procedure,furthermore, many inflammatory factor participate in this procedure, IncludingIL-1,TNF-αand PDGF-A. They destroy the dynamic balance of bone metabolism ,lead to bone destruction and abnormity of articulus.In Chinese medicine, RA belongs to the range of "arthalgia syndrome", it ismainly caused by deficiency of liver and kidney, malnutrition of the muscles andtendons, invasion of wind, cold, dampness, impeded circulation of qi and the blood,obstruction of blood stasis and phlegm in the channels, which lead to bone damageand deformity of joints. Modern pharmacology research confirm that Chinese drugs oftonifying the liver and kidney, promoting blood circulation and resoting flow cancontrol the formation of pannus, promote mature of Osteoblsat, constrain thedegradation of ECM, which lead to control bone destruction. Chinese drugs ofBiYuTang lies on the experience of national famous Professor Hu Yinqi, its functionis tonifying the liver and kidney, expelling wind and dampness, promoting bloodcirculation, activating the channels and relieveing pain.The TypeⅡcollagen-induced arthritis(CIA) is very similar with RA in manyways of clinical symptoms, pathological and histopathological changes.CIA is a bestanimal model that is used to study RA. Our previous experiments have confirmed that Chinese drags of BiYuTang can improve the level of OPG and decrease the level ofRANKL. Therefore, it can prevent the activation of Osteoclsat , improve the declineof Osteoclsat, relieve joint destruction.Objective: In our studies we plan to further elucidate the mechanism ofBiYuTang in curing bone erosion in RA by using the animal model of CIA rats, theCIA rats was feed with BiYuTang high dose,common dose and MTX for five weeks.HE staining observe pathological change Under high microscope, immuno-histochemistry method investigate the level of MMP-3,TIMP-1 and PDGF-A incartilage. Masson staining observe the difference of collagen fiber content incartilage. The aim of this study is to investigate the therapeutic mechanism ofBiYuTang in curing bone erosion in RA through these methods.Method:50 health SD male mice was divided into 5 groups(normal group,model group, common dose group, high dose group and MTX group in random eachgroup contains 10 mice. In the first part, the CIA rats was successful established byinjection the mixture of TypeⅡcollagen with Fraud' s adjuvants in ankle joint skin ofboth feet. After 1 week of immunization, the CIA rats were feed with BiYuTang highdose,common dose and MTX for five weeks except modle group. Common groupand modle group were feed equal volume Sodium Chloride.During this period, thechanges of the general status, swelling of the rats have been recorded at differenttime. After five weeks of treatment, the rats put to death and the serum was collected.HE staining observe the pathological change of ankle joint by microscope,immunohistochemistry technique investigate the level of MMP-3,TIMP-1 andPDGF-A in cartilage. Masson staining detect the expression of collagen fiber incartilage. The expression of MMP-3,TIMP-1,PDGF-A in cartilage was analyzed bycomputerized image system and the date was statistics by SPSS software.Results: (1) BiYuTang high dose,common dose could markedly reduce the degree of rat pedal swelling, improve general status. (2) The Immunohistochemistryand statistical analysis showed that the expression of MMP-3 in model group washigher than control group (P<0．01) . each treatment group could decrease theexpression of MMP-3 as compared to that in the model group. there was significantlydifference (P<0．01) . There was no significant difference between each treatmentgroup. TIMP-1 was contrast to the expression of MMP-3．The levels of PDGF-A inmodel group was higher than control group.After treatment, The levels of PDGF-Adecreased significantly in arthrodial cartilage as compared to that in the model group.there was significantly difference (P<0．01) . (3) Masson staining and statisticalanalysis showed that The levels of collogen fibril decreased significantly in arthrodialcartilage as compared to that in the model group. BiYuTang high dose,common doseand MTX groups could improve the expression of collogen fibril, There was nosignificant difference between each treatment group. But the curative effect oftreatment groups is BiYuTang high dose group briefly superior to MTX group andMTX group briefly superior to common dose group. (4) The pathologicals resultsshowed that synovialis hyperplasia and inflammation, inflammatory cell infiltration,formation of pannus and the erosion of cartilage and bones. Group of BiYuTang andMTX could lessen synovialis hyperplasia, restrain inflammatory cell infiltrate,inhibit pannus formation and relieve bone destrction.Conclusion: The result showed that Chinese drugs of BiYuTang had a defined effectin treating animal model of rheumatoid arthritis. The mechanism of inhibiting bonedestruction was related to the following factors, BiYuTang could decrease effectivelythe expression of MMP-3 , increase the expression of TIMP-1 , adjust thedisequilibrium of MMP-3 and TIMP-1 in arthrodial cartilage, accordingly relievecartilage destruction. BiYuTang could inhibit the level of PDGF-A in arthrodialcartilage, therefore, lessen synovialis hyperplasia, inhibit the formation of pannus,improve pathologic state of joint. The curative effect of BiYuTang was similar toclassics antirheumatic medication of MTX, moreover, it had obvious dose-effect relationship, high dose is superior to common dose in total therapeutic effect.