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Expression Of Eotaxin-3 In EG And The Effect Of Glucocorticoid

Posted on:2017-03-27Degree:MasterType:Thesis
Country:ChinaCandidate:L L HanFull Text:PDF
GTID:2334330488466580Subject:Internal Medicine
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BackgroundThe domestic and foreign literature reports about eosinoiophilic gastroenteritis are rare since the first report of Kajiser in 1937.EG is an uncommon gastrointestinal disease affecting both children and adults.In 30 to 50 years, there is no significant difference in the proportion between men and women.The incidence ratio of EG is about 5.5 times higher than eosinophilic esophagitis,Although it can involve any part of the gastrointestinal tract, the stomach and the proximal small bowel are the most common sites of involvement.,According to the involvement of the different site and layer, it can cause a variety of clinical manifestation.The clinical manifestation of EG is not specific and the most common symptoms are developmental arrest(especially in children),dysphagia, vomiting, abdominal pain, diarrhea and so on.The misdiagnosis rate and the misdiagnosis rate is high due to the lack of specific clinical manifestations and clinicians lacking deep understanding of the disease.Since the 90's of last century,it has attracted great attention of many scholars because its incidence is rising.Now it has been one of the hot research topics in recent years.Although there are a great deal of reports about the treatment,clinical manifestation, pathological diagnosis of eosinophilic gastroenteritis, but the etiology and pathogenesis of EG is not completely clear.the reports about this issue are limited.Because it is charactered of a large number of eosinophils infiltrating of the gastrointestinal tract, many scholars believe that the pathogenesis is related to invasion and immune responses of eosinophils and its mechanism may be concered with genetic and environmental factors at present.It is reported that about 81% of EG patients with atopic disease(atopic disease) coexist,about half of the patients with asthma(the most common, accounting for about 27.8%,)rhinitis, food, drug allergy and eczema or other allergic history.Current study found that eosinophils concentrated in local is closely related to eotaxin.Eotaxin which is considered to be the strongest chemotactic factor on eosinophil chemotactic activity is one of the C-C chemokine subfamily members.The gene family consists of Eotaxin-1, Eotaxin-2, Eotaxin-3.The researches have shown that Eotaxin-3 may be involved in the pathophysiological process of EG,Eosinophil chemotactic factor receptor(C-Cehemokinereeeptor3,CCR3) is the only receptor of eotaxin-3.Garcia Zepeda EA(1997) found that Eos cells express high CCR3,With high affinity between eotaxin-3 and CCR3, a series of biochemical reactions happen after banding together specifictly,including strong chemotactic migration of Eos to the sites of inflammation and a raise of eosinophils in the local area,This mechanism may be associated with Eos invasing in eosinophilic gastroenteritis,After the eosinophil activated and degranulation,it releases a series of inflammatory mediators,thus lead to the physiological effects of Pathology.At present, most people think that eosinophilic gastroenteritis is an allergic disease and it is closely related to genetics and environment. Glucocorticoids is the main drug for the treatment. But the side effects for long-term use is obvious and it is easy to relapse after drug withdrawal.Now because of lacking of specific and effective non-invasive biomarkers,the assessment for the severity of inflammation and the treatment of EG is mainly based on endoscopic examination.Eosinophil is the most important effector cells of EG,Eosinophil chemotactic factor is closely related to the occurrence and development of the disease and the current study has found that only eotaxin has specific chemotaxis on eosinophils among all the chemokines in eosinophilic gastroenteritis. Because eotaxin-3 belongs to eotaxin gene family,Study on the related animal experiments have shown there is high expression of eotaxin-3 in serum and tissue of EG mice,But the expression of eotaxin-3 in serum and tissues of patients with EG is rarely reported,To investigate the role of eotaxin-3 in the pathophysiology process of EG and the mechanisms of glucocorticoids in the treatment of EG,we explore the expression level and significance of eotaxin-3 in serum and tissue of the subjects with Eosinoiophilic gastroenteritis and the the effect of glucocorticoid in this study. By improving the understanding of the eotaxin-3 in eosinophilic gastroenteritis,we can Inhibit the protein related with eotaxin-3 expressing,or use CCR3 antagonists to bolck the effective combination between eotaxin-3 and CCR3,which block Eos in tissue were recruited.This may become a new effective method for the treatment of EG.Based on these, we can search for an nonintrusive biomarkers for the evaluation about treatment response of EG without the need for invasive surveillance endoscopies providing a theoretical basis at the same time. AIMTo study the expression level and significance of eotaxin-3 in serum and tissue of the subjects with Eosinoiophilic gastroenteritis and the the effect of glucocorticoid. METHODSA total of 48 subjects with EG diagnosed for the first time and 24 healthy controls were included. Patients with EG were randomly divided into untreatment group and prednisone group on average.The expression of Eotaxin-3 was measured by enzyme-linked immuno sorbent assay(ELISA) techniques in the serum and tissue of all the subjects. RESULTS1)The expression level of Eotaxin-3 in serum and tissue was significantly higher in EG group than in the controls(P<0.05).2)Comparison of before and after treatment,the expression level of Eotaxin-3 in serum and tissue are signifieant difference in the treatment group(P<0.05),yet the difference was not statistieally significance in placebo group.3)The number of infiltrating Eos and the expression of eotaxin-3 in serum and tissue was signifieantly positively eorrelated in EG group with a statistieal significance. CONLUSIONEotaxin-3 may paticipates in the pathophysiology processes of EG;Glucocorticoid palys an important role in downing regulation the expression of Eotaxin-3,then weak the eosinophil chemoattractant and activation in ordor to reduce the inflammation, and this is probably one of the mechanisms of glucocorticoid in the treatment of EG;For the treatment of Eotaxin-3 function may become a new target for the treatment of EG;The date of this study show that Eotaxin-3 in serum may have some values to assess the inflammation degree and therapeutic result as noninvasive biomarkers.
Keywords/Search Tags:Eosinoiophili gastroenteritis, Eosnophils count, Eosinophil chemotactic factor-3, Glucocorticoids
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