The Relationship Between The Expression Of VEGFmRNA In PBMC Of RA And ILD

ObjectiveRheumatoid arthritis(RA) is a commonly seen functional disease, which can cause deformity,hereditary,environmental and many other factors attribute to this. The incidence of this disease is approximately 1%.RA is an autoimmune disease specifed for its continuous,chronic arthrosis and synovial membrane inflammation,the synovial membrane proliferate into pannus,in which the feature of the growth is similar to tumor,and which leads to degradation of the cartilage and damage of the bone. The expansion of the synovial lining of joints in rheumatoid arthritis (RA), and the subsequent invasion by the pannus of underlying cartilage and bone, necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. New blood vessel formation - 'angiogenesis' - is now recognised as a key event in the formation and maintenance of the pannus in RA. Although many pro-angiogenic factors have been demonstrated to be expressed in RA synovium, the potent pro-angiogenic cytokine-vascular endothelial growth factor (VEGF) has been demonstrated to have a central involvement in the angiogenic process in RA.Interstitial lung disease(ILD) is the commonest manifestation secondary from RA . 47% patients of RA have lung despair,30% of which have malformed X-ray. The initial factor of lung impair is not clear at present,but it associate with hereditary susceptibility,virus inflammation and malformed immune function. Many factors impaired aveole epithelium and capillary endothelium cells,which lead to the activation of macrophage,the infiltration of mononuclear cell and neutrophil,inflammatory cell and its releasing factors mediate the the impair of the lung. At present many cell factors mediated immunomechnism is currently considered as the foundation of the occurrence and development of the disease,and is the important factor in the pathophysiological process of fibrosis and angiogenesis.Vascular endothelial growth factor(VEGF) is a mitogen which affect the vascular endothelial cells directly,and is the strongest vascular growth promotion factor occurrently, which is closely associated with angiogenesis. The study in the culture of the synovial fibroblasts showed VEGF is expressed very high in synovial membrane tissue supernantants. It is found with immunohistochemistry that VEGF peptide is existed in the macrophage and capillary endothelium cells of inflammatory synovial membrane. So RA may play an important role in the pathogenesis of RA. The proliferation of synovial membrane cell in RA is due to the imbalance between angiogenesis growth factor and angiogenesis inhibitor. As angiogenesis growth factor, VEGF play an important role. Many cells in the body can endocrine VEGF,it is expressed high in the lung as usual,mainly in the type II alveole cells, macrophage and neutrophil,and is very crucial to keeping the stabilization of the vessel structure and alveolous blood-gas barrier. There is much angiogenesis in the pathogenesis of ILD. and it may play some role in ILD.The affect of VEGF in which RA leads to ILD has not been reported,at present. We study the expression of VEGF in PBMC of the patient with arthritis, to investigate the role of VEGF in the pathogenesis of RA,and the related functions in which RA leads to ILD.Methods and materials1.The subject 64 patients of RA were divided into three groups:single RA35, ILD secondary from RA29,controls20 according to whether the ILD is existed.2.Draw 5ml blood off from perivenous into heparin anticoagulant tube in the morning,dilute with equal PBS,separate the PBMC with Ficoll density gradient centrifugal, add 1ml TotalRNA extraction reagent to dissolve completely,store at -70℃refrigerater for detection. Samples are incubated for 30 minutes after taken out.3. Examine the expression of VEGFmRNA in PBMC with semi-quantitative RT-PCR method. The expression of VEGFmRNA is caculated by the ratio with the internal controlβ-Actin. All data are analyzed with software spss13.0.Results1.The expression of VEGFmRNA in PBMC of RA patients was significantly higher than the controls,the difference is statistically significant(p<0.05).2.The group which RA leads to ILD was significantly higher than the single RA, the difference is statistically significant(p<0.01).3.The expression of VEGFmRNA in PBMC of single RA patients was significantly higher than the controls,the difference is statistically significant(p<0.01).4.Analysis of relativity between VEGFmRNA and laboratory index:The relative coefficient of VEGF and ESR is 0.385(P<0.05),has positive relativity. The relative coefficient of VEGF and RF is 0.206(P>0.05). The relative coefficient of VEGF and IgG is 0.125(P>0.05). The relative coefficient of VEGF and PLT is 0.134(P>0.05) .The relative coefficient of VEGF and HB is 0.185(P>0.05).Conclusion1.The expression of VEGFmRNA in PBMC is elevated which showed that VEGF plays an important role in the pathogenesis of RA.2.The expression of VEGFmRNA is higher especially in the procession of ILD secondary from RA,which indicate that VEGF may play a role in the promotion of lung fibrosis.3.The expression of VEGFmRNA is relative to ESR positively,suggest that it correlates with the activity of RA,and can act as an actitive index of RA.