Intervention Effects And Mechanisms Of Qingluotongbi Granule On Bone Destruction Of Rheumatoid Arthritis

QingLuoYongBi Granule(QLT)has therapeutic effect on rheumatoid arthritis(RA).The destruction of sclerotin plays an important role in the pathogenesis of RA,therefore, we studied the intervention of QLT in that process and made preliminaryinvestigation on its mechanism.The study was divided into 3 parts:Part 1 To research the influence of QLT on sclerotin destruction in collagenicinflammatory arthropathy(CIA).(1) Continuing administrated QLT to CIA rats for 49days since the 7th day after the CIA rat model had been successfully setup to observesclerotin destroy of each group by X-ray after the last administration;(2) To observe theinfluence of cultivated synovial cell supernatant and QLT-contained serum of each groupCIA rats to the proliferation of exoteric cultivated normal rabbit Cartilage cell,respectively, and the influence of cultivated synovial cell supernatant and QLT-containedserum of CIA rats to the expression of TP, NO and iNOS in cartilaginous cell supernatant,respectively. Results: the inhibition of pathologic histological changes was observed inthe three groups of CIA rats, low(3.6g/kg), middle(7.2g/kg) and high-dosage(14.4g/kg)groups. Meanwhile, there were some effects in improving the decreased bone mineraldensity (BMD), the broadened articular cavity interspace and the destroyed articularstructure of CIA rats. The proliferation ability of cartilage cells and the synthesis of totalprotein were increased by the cultivated synovial cell supernatant of CIA rats given7.2g/kg and 14.4g/kg QLT, and the iNOS expression and NO content were decreased.The proliferation ability of cartilage cell and the synthesis of total protein weresignificantly increased by QLT-contained serum of CIA rats given 14.4g/kg QLT,however, there was no effect on iNOS expression and NO content. The above resultsshowed that QLT had the protective effect on sclerotin destruction of CIA rats. This kindof effect would be related to the promotion of the cartilage cell proliferation and theinhibition of synovial cell producing inflammation factors.Part 2 To study the effect of QLT-contained serum on the growth of osteoblast (OB)and osteoclast (OC). (1) Cultivating neonate rat cranial bones OB in virto to investigatethe influence of proliferation effect of cultivated normal neonate rats cranial bones OB and the content of AKP in the cultivated supernatant by QLT-contained serum; (2)Cultivating neonate rat long bone OC in virto to observe the influence of the growtheffect of neonate rat long bone OC by QLT-contained serum. Results: the OBproliferation effect and the ability of AKP were obviously increased by QLT-containedserum of rats given 7.2g/kg,14.4g/kg QLT. The QLT-contained serum of all the threegroups, low(3.6g/kg), middle(7.2g/kg) and high-dosage (14.4g/kg) groups,inhibited OCsignificantly. These results showed that QLT administrated extraneously could promoteOB proliferation and inhibit OC growth to protect the decreased bone density which wascaused by the OC activation and OB disability. This protective effect would be related tothe enhancing of OB proliferation, increasing the AKP ability, inhibiting OC growth andmodifying the balance of OB-OC by QLT.Part 3 To investigate the influence of QLT-contained serum on receptor activator ofnuclear factor kappa B ligand (RANKL) of peripheral blood lymphocyte in RA patientsin active phase. Adding CD3-FITC and RANKL-PE in whole blood of RA patients orhealthy volunteers to observe the RANKL differences between patients and healthyvolunteers. This process was measured by FACS Calibur flow cytometry and analyzed byCell quest. To observe the influence of QLT-contained serum on RANKL expression ofperipheral blood lymphocyte in RA patients. Results: RANKL expressed more in activestate RA patients than that in healthy people. QLT-contained serum from rabbit given14.4g/kg QLT could obviously inhibit the peripheral blood T lymphocyte RANKLexpression of RA patients stimulated by PHA in virto. Above results indicated that QLTcould prevent OC differentiation and maturity through inhibiting RANKL expression inperipheral blood lymphocyte to make some therapeutic effect on sclerotin destruction inRA.Conclusion: The protective effect QLT on sclerotin destroy was probablycontributed to its ability on modifying RA inflammatory, and thus to modify theunbalance of OB-OC function which was caused the sclerotin destroy. Meanwhile, thiseffect would have some relationship with the inhibition of high RANKL expression inactive RA patient peripheral blood lymphocyte.