| introductionRheumatoid arthritis ( RA) is a chronic, inflammatory, systemic disease that produces its most prominent manifestations in the diarthrodial joints, develops in peripheral joints. The main pathological change of Rheumatoid arthritis is persistent and progressive synovitis , inflammatory cell infiltration and pannus, The etiology, and pathogenic mechanism of RA are still unknown. Until now, the effection of existing therapy is far from satisfying. But as proved by many researches , the induction of apoptosis of the abnormal synoviocytes hyperplasia may become an effective method to treat RA. Among the inflammatory cytokines, IL - 1 and TNF - aplay a key role during the progression of the disease.Apoptosis is programmed cell death regulated by genes. The destruction of cartilage and bone is primarily caused by the activation and hyperplasia of synoviocytes. The pathogenesis of RA is closely related with the course of apoptosis, synoviocytes hyperplasia rooted in the comparatively deficient synoviocytes apo-tosis. transcription factor (NF -κB) is a central mediator for the gene expression induced in cells by pathogens or inflammatory cytokines, and is known to play an important role in development of the immune system. It has been recently shown NF - κB activates an anti apototic response by inducing gene transcription. Training content (objective, benefit and expected impact) To achieve our objectives, a TNF responsive cell line containing an inducible inhibitor of NF -κB will generated. When the NF - κB inhibitor alpha (a transdominant negative version resistant to signal induced proteolysis) is induced and the cells exposed to TNF, apotosis will be triggered. In the absence of inhibitor, NF - κB will beinduced and transcription of the anti - apoptotic genes will protect the cell from the TNF induced apoptosis.Arsenic prescriptions are widely used as apoptosis - inducer, most of the studies on the anti - tumor effection of arsenic were focused on apoptosis. In the pathogenic mechanism, the aggressive synoviocytes hyperplasia is the main change of synovitis. The growth and behavioral pathology of synoviocytesis similar with the characteristics tumor tissue. So Arsenic prescriptions may induce the synoviocytes apoptosis. Our experiment is based on this theory and aimedObjectivesUsing By observing the Arsenic Trioxide - induced synoviocytes apoptosis in the rats with adjuvant - induced arthritis , explore the possible mechanism of treating RA with Arsenic Trioxide .MethodsWistar rats, female, 4 wistar rats wre chosen randomly among 40 of them as control group, others as treatment group. Arthritis was induced by righthind paw hypodermic injection of complete Freunds adjuvant (CFA) 0. 1ml. The immunity was reinforced 20days later by repeat the injection as above. 30 day after the first injection, several rats with arthritis which the arthritis scale is above 2 points were elected, then randomly divide them into two groups: model control group and arsenic trioxid treatment group. 3 days after the model s ere ready, the rats in treatment group were injected with arsenic trioxid fluid 4mg/kg,/d for 7 days. All of the rats were killed by anaesthesia 44 days after the injection. The joints were exposed and fixed in 4% paraformaldehyde solution, decalcified by mixed acid, wraped up with paraffin wax, then cut into slice.Measure the thickness of righthind paw pad and the sum of longitudinal and traverse diameter of righthind ankle. Calculate the dsgree of swell. Pathological HE stain: selected tissue slices were dried overnight. After dewaxing, rince, stain and differentiation. , the slices were observed under microscope and thephotos qere taken.Immunohistoloical evaluation: operate according to the instruction of SP test kit,finally developed color with DAB color - developing rest kit. after restain, differentiation, dehydration and envelop, , the slices were observed under microscope and the photos qere taken. Analize the image by image analyzer, measure the average gray scale. Analize the data by statistics software Spss 10. 0.ResultsThe The joints swell degree on the rats in experiment group which model were made successfully is marked increased compared with those in control group. ( p <0. 05). After treated with arsenic trioxide, The joints swell degree on the rats in treatment group is marked lower than those in model groupand normal group. Pathological HE stain:the synovial structure of joint cavity in normal control group is clear, no hyperplasia and lymphocyte has been found, plasma cell infiltration is unconspicuous ; while the synovial tissue on the rats in AA model group became thick and pannus were formed, the layers of synoviocytes increased to 6 - 8, and a large amount of inflammatory cell infiltration can be found. The pathological change of synovial tissue on the rats in arsenic trioxide group is much less sever then those in the model group. , the layers of synoviocytes increased to 3 -4,and the arrangement of synoviocytes was disordered.Immunohistoloical evaluation; The intensity of synovial NF - κB positive stain in AA model group is marked higher than that in normal control group. After Treated by arsenic trioxide for 1 week, The synovial expression and activation of NF - kBui arsenic trioxide group are decreased obviously, but did not recover to the normal level, the average gray scale calculation showed that there was marked difference among the there groups.ConclusionArsenic trioxide can inhibit synoviocytes differentiation and induce synoviocytes apoptosis, thus alleviate the swell of synovial tissue. That maybe due to...
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