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Identify An Increased Expression Of Carbonic Anhydrase ? In The Synovium Of Patients With Ankylosing Spondylitis

Posted on:2012-08-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:H ZhangFull Text:PDF
GTID:1484303353453814Subject:Surgery
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Ankylosing spondylitis is a chronic inflammatory disease.It pathogenesis is remains unclear,which may involve many factors,such as genetic factors,environmental factors,and so on.In the aspect of genetic factors,after the initial discovery of HLA-B27,other major histocompatiblity complex genes(MHC) and non-MHC genes associated with AS were reported gradually.For environmental factors,it is thought that certain microorganism may participate in the pathogenesis of AS.With the further understanding of the association between the infection and immune disease,especially infection and spondyloarthropathy,the role of infection in AS has gained more and more attention.Ankylosing spondylitis is a highest inherited disease, lately about ankylosing spondylitis home department and twin studies revealed the genetic susceptibility gene mode. HLA B-27 was found to be strong correlation of ankylosing spondylitis, since many evidence indicate that HLA B-27 directly involved in the pathogenesis of ankylosing spondylitis yan. Certainly HLA B-27 molecules are ankylosing spondylitis primary relevance composition, its direct evidence from human HLA B-27 in transgenic rats. Many scholars have turned their attention to put forward immunity abnormalities mistake folding theory, surface the same type dimers heoryhypothesis. Bacterial infection induced ReA has been a large study confirmed, but the position in AS microbial infections is still in exploration. Currently proposed and AS the main have possibly related disease pneumonia crayresearch bacteria, salmonella bacteria intestinal G-bacteria such AS garment former body, etc. The chlamydia has confirmed the endogenous fragments produced in vivo can be deferred by the HLA B27 on cells surface. In addition, chlamydia trachomatis 610 coding genetic products can also be deferred B2705 cells in, and chlamydia trachomatis certain gene sequences and the body of some protein contains sequence similar, these series also includes HLA B27 combining base sequence. So the research results indirectly indicates tha there is a correlation beween chlamydia and AS. About chlamydia and AS study is less, the early main positioning albright eye chlamydia, but failed to clear its relevance, pending for further research. Early for pneumonia crayresearch AS bacteria and the research of scholars about AS many patients with excrement, serum etc have several detection, because detection method and the object of study are different, so the conclusion has been debating.Objective The most distinctive features of ankylosing spondylitis (AS) are new bone formation and bone resorption at sites of chronic inflammation. The present study applied a proteomics approach to identify novel AS-specific proteins by simultaneously comparing the expression profiles of synovial membranes from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA). Methods Total proteins extracted from synovial tissues (n=10 for each disease) were separated by 2-D electrophoresis, and the proteins with significantly increased expression in the AS samples were subjected to MALDI-TOF/TOF-MS analysis. The results were verified using western blotting and immunohistochemistry. Results Compared with RA and OA tissue samples, the proteomics approach revealed significantly increased expression of carbonic anhydrase I (CA1) in the synovial membrane of patients with AS. Immunohistochemistry and western blotting analysis confirmed the above finding. Conclusions It has been reported that CA1 catalyzes the generation of CaCO3 precipitation. Many evidences also indicated that carbonic anhydrase stimulates bone resorption. Hence, over-expression of CA1 in synovium of AS may promote improper calcification and bone resorption, two essential steps of AS pathogenesis. This topic research framework as follows:CA1 can promote carbon dioxide and water to combine into bicarbonate. The Parissa think that CA1 participate in carbon dioxide hydration effect and calcium carbonate formation process. They add CA1 and calcium chloride into Tris buffer, and then add carbon dioxide. Along with the CA1 concentration and temperature elevated,it is found that the CA1 promote the formation of calcium carbonate precipitation. Through the experiment,we found that carbon anhydride enzyme purificated from the citric acid can promote formation of calcium carbonate precipitation. The results indicate that CA1 not only can promote the hydration reaction of carbon dioxide.,but also promote calcium carbonate precipitation formation. Therefore, excessive expression of CA1 in AS synovial may lead to calcification of the tissue. one of the pathology of AS is that there is new sick bone formation in chronic inflammation area.The major component of bone calcium phosphate and calcium carbonate. CA takes part in the hysiological and pathological activities of calcification and mineralization. The shell of bird is made of organic matrix and calcium carbonate In the bone formation process, the osteoblast secrete a kind of matrix called bone samples,it is jelly made of the collagen and glycosaminoglycan.the pathogenic mechanism of AS is unclear, it is thought that s genetic, inflammation or infection many factors all may take part in the the pathogenic mechanism of AS. In the urrent study,between the HLA B27 and AS, there is a close relation B27MHC gene and the numerous than the MHC genes put forward the irulence mechanisms of the exploration for AS providing a wide range of ideas. Environmental factors, chlamydia and other microbes and the relationship of the spine stanching the onset of for AS proposed research provides a new clue. However, in the pathogenesis of clear microorganisms, and the pathogenic mechanism research needs to be more in-depth research. We Believe that through the comprehensive analysis of genetic, environmental factors such AS the interaction, AS pathogenesis in the near future will be uncovered, etiology research breakthrough will bring comprehensive innovations for the diagnosis, treatment of AS.
Keywords/Search Tags:Ankylosing spondylitis, Genetic, infection, Hunman leucocyte antigen B27, Chlamydia, Carbonic anhydrase?, Calcification, bone resorption
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