The Role Of Peroxisome Proliferator-activated Receptor-γ In Asthmatic Mice Airway Remodeling

Objective:1. Established kunming mice to chronic asthma airway remodelingmodel by OVA sensitized and excited.2. Counted the number of the PeroxisomeProliferator-activated Receptor-γ(PPAR-γ) positive cells in lung tissue, detected theeosinophil counts,the IL-13and VEGF level in bronchoalveolar lavagefluid(BLAF)and observed the pulmonary histopathology of lung tissue, the changes ofairway morphology in the asthma group, the intervention group and the control group,explore the role of PPAR-γ in the bronchial asthma airway remodeling pathogenesis andthe effect of early intervention.Methods:30female SPF Kunming mice(Provided by the Experimental AnimalCenter of Dalian Medical University) which4~6weeks old,18~22g, were dividedinto three groups randomly as follows: asthma group, rosiglitazone treatment group, andnormal control group, each group10mice. Established asthma model with eggalbumin(OVA) immunization: in the first0,7,14days, gave the mice of asthma groupand rosiglitazone treatment group with20μg OVA+150μl AL(OH)3+50μl NS(100mg/L)intraperitoneal injection.The28,29,30days,gave the mice of asthma group50μlOVA-NS (2g/L) intranasal stimulated. At the30~60days, ultrasonic atomizing inhaled2%OVA saline atomization fluid in a homemade atomizer box every day, lasting30minutes, rosiglitazone treatment group mice rosiglitazone5mg/Kg gavage before theatomization. Normal control group used normal saline as the same way like asthmagroup. After24hours from the last atomization, cervical dislocation executed all of themice. After drawn the materials in each group, count eosinophil which in BALF byoptical microscope, detected IL-13and VEGF in BALF by ELISA, observated thepathological specimens, measured the Pbm, Wat, Wam and ASM by pathological image,measured the numbers of PPAR-γ in the lung tissue by immunohistochemical staining.The experimental data are analyzed by SPSS11.5software. Results:1. During the sensitization both of asthma group and rosiglitazone treatmentgroup,appeared disparity dysphoria, tachypnea, Scratching nose, reduced activity,urinary and fecal incontinence, lose luster Etc. But after intervention, the symptoms ofrosiglitazone treatment group were relieved. Normal control group had not thesesymptoms.2. Observation of pulmonary histopathologically: Observed at high magnification,asthma group appeared airway wall thickening, lumen deformation, respiratory tractepithelial cell shedding, mucus secretion increased, airway smooth muscle thickening,vascular wall thickening, submucosa and wall surrounding inflammatory cell infiltration.The rosiglitazone treatment group were observed epithelial cells occasionally shedding,the mucosa is relatively smooth and Completeness, the inflammatory cell infiltratedwere significantly lighter than asthma group. The normal control group trachea andalveolar structure were normal, bronchial epithelium Completeness, did not sawinflammatory cells.3. Analysis of airway morphology: the WAt/pbm of asthma group, rosiglitazonetreatment group, and normal control group are15.25±1.43μm~2/μm，11.94±1.26μm~2/μm，10.79±2.20μm~2/μm, WAm/pbm are4.17±0.70μm~2/μm，2.88±0.63μm~2/μm，4.02±0.77μm~2/μm； thickness of ASM are15.7±2.0μm，10.7±1.3μm，5.1±1.8μm。The WAt/pbm，WAm/pbm，thickness of ASM of asthmagroup higher than rosiglitazone treatment group and normal control group (P<0.01), thedifference has statistically significant; rosiglitazone treatment group higher than normalcontrol group (P<0.01), the difference has statistically significant.4. The count of eosinophils in BALF: the asthma group is12.32±0.91×106/ml, therosiglitazone treatment group is7.13±0.41×106/ml, the normal control group is0.50±0.08×106/ml. The asthma group higher than the rosiglitazone treatment group andnormal control group (P<0.01), the difference has statistically significant; therosiglitazone treatment group higher than normal control group (P<0.01), the differencewas statistically significant.5. The IL-13、VEGF level in BALF：the IL-13of the asthma group, rosiglitazonetreatment group and normal control group are59.82±16.98pg/ml,40.25±3.87pg/ml,35.05±6.67pg/ml，the asthma group higher than rosiglitazone treatment group andnormal control group (P<0.01), the difference has statistically significant; rosiglitazonetreatment group higher than normal control group (P<0.01), the difference has statistically significant. The VEGF of each group are246.14±15.77pg/ml,32.75±2.45pg/ml,85.40±8.32pg/ml, the asthma group higher than rosiglitazonetreatment group and normal control group (P<0.01), the difference has statisticallysignificant; rosiglitazone treatment group higher than normal control group (P<0.01),the difference has statistically significant.6.The counts of PPAR-γ positive cells in lung tissue by immunohistochemicalstaining: the asthma group is13.10±0.82， the rosiglitazone treatment group is18.40±0.67, the normal control group is7.50±0.72, the rosiglitazone treatment grouphigher than asthma group and normal control group (P<0.01), the difference hasstatistically significant; the asthma group higher than the normal control group (P<0.01),the difference has statistically significant.Conclusion:1. Kunming mice were established ideal model of asthma by OVA sensitized andrepeatedly stimulated, also with the airway inflammation and airway remodeling;2. The expression of PPAR-γ was highly in asthma mice’s airway epithelial andinflammatory cells, PPAR-γ interpose the airway remodeling;3. The actived PPAR-γ can reduced the amount and inhibit the function of Th2cellin the level of inflammation，airway smooth muscle hyperplasia, vascular remodelingcorrespondingly, thus intervene the airway remodeling of asthma;...