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Dynamic Expression And Significance Of IL-17and IL-6in The Rats Of Bleomycin-induced Pulmonary Fibrosis

Posted on:2013-07-28Degree:MasterType:Thesis
Country:ChinaCandidate:H Q ZhangFull Text:PDF
GTID:2234330371477719Subject:Geriatrics
Abstract/Summary:
Background:Interstitial lung disease involve in the pulmonary mass,alveolar,and (or) thin bronchial diffuse lung disease. The clinical manifestations include unexplained chronic exertional dyspnea,with cough,lung burst and tone clubbing. Lung function expressed as a progressive restrictive ventilatory dysfunction and diffusion barriers.In recent years,the prevalence or incidence were an upward trend,and the prevalence is proportional with age The pathogenesis of pulmonary fibrosis is not very clear. The main changes of pulmonary fibrosis is alveolar inflammatory in the early.Cytokines and cytokines networks play an important role in the stage of inflammatory injury,which is the incidence of pulmonary fibrosis in the early.IL-17can mediated mobilization,recruitment and activation of neutrophil,and effectively mediate inflammation. IL-17can produced pro-inflammatory cytokines (eg. IL-6and TNF-a),activated NF-κB and involved in pro-inflammatory response.When IL-6and TGF-β work together,initial T cell differentiate to Thl7cell which can produce IL-17.IL-6is a multifunctional cytokine,which is an important regulatory factor to body’s immune-nerve-endocrine.Its biological role include:1.Immune function;2.Acute phase response;3. Inflammatory response;4.Anti-tumor effects.In this study,using bleomycin-induced pulmonary fibrosis model study the dynamic variation of IL-17and IL-6in the process of pulmonary fibrosis and explore the pathogenesis of pulmonary fibrosis,to provide new ideas for diagnosis and treatment of pulmonary fibrosis.Objective:1.Observe the the lung tissue pathological changes of bleomycin-induced rat pulmonary fibrosis.2. Measure the content of hydroxyproline (HYP) in lung tissue in the process of pulmonary fibrosis in rat.3.Determine the levels and dynamic changing of IL-17and IL-6in serum of rats.Methods:Seventy-two healthy male Wistar rats (200g±20g) were divided into normal control group,model group and dexamethasone treatment group randomly.Each group contain twenty-four rats. The pulmonary fibrosis model was established by intratracheal injection of bleomycin (BLM:5mg/Kg) with rats of model group and dexamethasone treatment group. While rats of the normal group injected with saline. The next day,rats of treatment group were injected with dexamethasone(lmg/kg) in intraperitoneal every other day. The rats of normal control group and model group were injected with saline.Three groups of rats were sacrified at3rd,7th,14th and28th days after modeling.Holding the lung tissue and paraffin-embedded sections,Staining by HE method to observe the pathological changes and assay the content of hydroxyproline content by alkaline hydrolysis; Measure the levels of IL-17and IL-6in serum with enzyme-linked immuno sorbent assay (ELISA).Results:1. In model group,lung tissue biopsy showed the dynamic process of change from alveolitis to fibrosis gradually.The degree of alveolar inflammation of the seventh days is the most serious and there are inflammatory cell infiltration,alveolar septa become widened then alveolar inflammatory reduced gradually and fibrosis increased gradually;The trend of pathological changes in dexamethasone treatment group is same with the model group,but lighter than the model group.2.The levels of hydroxyproline in model group and dexamethasone treatment group in lung tissue increased gradually with time.The levels of model group was significantly higher than the normal control group (P<0.05),and dexamethasone treatment group was decreased than model group (P<0.05).3.The levels of model group’s IL-17and IL-6which were determined by ELISA in serum was significantly higher than the control group at all time points,and reached a peak on the7th day (P<0.05),then levels of IL-17decreased gradually,but still higher than normal on the28th day(P<0.05). Dynamic changes of IL-6in serum were same as IL-17in serum basically.4.Using the Spearman rank correlation analysis make correlation analysis between rat alveolar inflammation and the content IL-17in serum,correlation coefficient r=0.902(P<0.01).showed that rat alveolar inflammation was positively correlated with the content of IL-17in serum.Conclusion:1.In this study,the bleomycin-induced pulmonary fibrosis model were successfully established.2.IL-17and IL-6were high expression of pulmonary fibrosis model group which is related of inflammatory response in the early and may be involved in the formation of pulmonary fibrosis.
Keywords/Search Tags:pulmonary, fibrosis, IL-17, IL-6, hydroxyproline
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