A Study On Related Genes Expression Of Asthma In Children And Airway Remodeling

The characteristic of bronchial asthma (BA) is chronic airway inflammation,airway hyperresponsiveness and airway remodeling. Asthma is involved ingenenation and environment. In 2000, GINA committee estimated that the patientsof asthma are about 300 millin in the world. The attact rate of asthma is0.5%³.34% in the children of our country, and 50% children of asthma could befinal diagnosis after 3 years in illness. Airway remodeling is the importantmechnism of refractoriness asthma. Airway hyperresponsiveness, airwayinflammation and airway remodeling are related each other .At the moment,some scholars raised that airway remodeling arised on the early stage ofasthma ,that is different to formerly . Now the mechnism of airway remodeling isnot clarified enough. Asthma is hereditary disease about certain genes. IL-12,β₂-AR,LTs-Receptor genes are related to asthma . Human are understanding themechanism of asthma from molecular level to level of gene.. Immunenetwork theory emphasized that immnologic system is unity ofopposites ecomomy which is inter communication and interrestrict of everycytoclone . BA is a kind of allergic disorder which is induced by immune, rarely10 kinds of cell, 20 kinds of cytodine , 50 kinds of active medium participate in it,and it set up a immunemetwork of cellular level and molecular level. Thatpathogenesy is correlated to immunology.This topic made use of the method of molecular biology, detected the geneticexpression of IL-12 and β2AR;Contrasted the relation of genetic expression andgently, middle, severious grade asthma;Constructed the inflammatory cellpopulation in BALF;Invested the express abnormality ofα-SMA,Collagen Type1 about airway remodeling rat in cell and molecule level.;Observated theinfluence of Ventolin, Singulair, Fluticasone and contrasted the impaction;Contrasted the impact to drug effective in different time of dosage;To understandthe biological function and express of IL-12 in rat airway remodeling. Our takedthe related genes of children;Analysised the data of immunocytochemistry;desc-ripted the change of appearance and function in the cell and framework..一,The genes express and correlation of IL-12, β2AR in the PBMC ofasthma children. The genes of IL-12, β2AR, CysLT1-receptor are importance inBA. IL-12 is cytokine which caused immunological regulation and inflammation;β2AR is adrenergic neuroreceptor of autonomic;CysLT1-receptor is mediumreceptor of phlegmasia. The experiment indicated that cytokine and receptor haddependability. The gene express level of IL-12, β2AR in the children of asthmais obviously lower than mormal, P<0.01, the different is significance;The geneexpress level of IL-12 is positive correlation toβ2AR in PBMC of asthmachildren , P<0.01;The express level of CysLT1-receptor is regative correlation toIL-12, β2AR in the PBMC of asthma children, P<0.01;The gene express ofβ2AR is related to the degree of asthma, P<0.01, they are negative correlation;Theexpression of IL-12 is independence to the degree of asthma, p>0.05.There are dependability among IL-12 , β 2AR and CysLT1-receptorexpression in asthma children. But, we did not know the overall and identifymechanism about dependability, yet. A lot of experiment confirmed thatcombinated administration was better than single and fraction dosage aboutFluticasone and Ventolin. Fluticason can up-regulated the expression of IL-12, vizthat there are synergistic effect between IL-12 andβ2AR. The process of illness islike the course of life, that is multiplicity and contrary. But that procedure has rulein it.二,Preanre the asthma and airway remodeling model of ratOur experiment established Wistar rat model of asthma and airwayremodeling succeedly by allergizing and provocation of OVA. Chronicinflammation and dyspnea with rapid and short breath repeatedly is a long-termprocess. The chronic inflammation of airway had continued long time whenasthma could ne diagnosed in clinic. Consequently, we could presumed thatasthma and airway remodeling is simultaneous.The cellar score, leukomonocyte, eosinophilic and mast cells step up in thegroup of model, P<0.01, the difference os significance;The blood serum level ofIL-12 in the group of model rat is lower than mormal, P<0.01;Ciliated epithelialcells, fibroblast and smooth muscle cell are changed about different digree in therat aerway of model, that cued inflammation and hyperplasy;Airway smoothmuscle thickening and leukomonocyte infiltrating in the rat airway of modelgroup;α-SMA andâ… -Collagen had homoexpression in lung, P<0.01. Thesignificance of remodeling is that constitution and function are difference betweenrepaired airway. â… -Collagen is a powerful index of airway remodeling. Theappearance of airway remodeling is the change of extracellular material.Expecially, basal membrane turned to thickening and transparence.â… -Collagen isimportant in cancellated material which caused basal membrane thickening.三,Compared the intervention effective of drug to airway remodelingFluticasone, Ventolin and Singulair are significance on controlling asthmaand airway remodeling in clinical application. Our test verified that there were notmanifest quantition diversity about inflammatory cell between the first groupwhich inhalded Fluticason and Ventolin and the second group which lavagedSingulair, P<0.01;The first group could utility raised the level of IL-12 in ratblood serum than the second group, P<0.01;The second group of drug couldpretected construction and function of ciliated epithelial cells , fibroblast andSMC better than the first group , decreasing hazard of airway;The first group ofdrug inhibited the airway smooth muscle thickening, inflammatory cell infiltrationand prevented airway remodeling. α-SMA expressed on the airway smoothmuscle, â… -Collagen expressed nearly smooth muscle and blood vessel. Thesecond group of drug expressed moreα-SMA and â… -Collagen than the firstgroup, P<0.01;The first group of drug had more ascendancy in soothinginflammation and inhibiting the chang of struction in airway than singulair.å››,The Singulair's influence to airway remodeling in different dosage timeEarly diagnosis, early medication are rout treatment policy. Our experimentindicated that early treatment lavaging Singulair to rat asthma and airwayremodeling model would aggravated gasping;dosage in advanced stage couldmore raised the level of IL-12 than early dosage or undosage, and increasing thenumbers of inflammatory cell in rat BALF, P < 0.01, the distinetion issignificance;Early dosage aggravated damage of airway , more liukomonocyteinfiltrated in lung, and thickening smooth muscle. α-SMA and â… -Collagenexpressed more than advanced stage dosage, P<0.01. At present , Singulair'stherapeutic effect hasnot determined, it was applicated to prevent and long termtherapy for 2-14 years old children. Through our test's outcome and relatedliterature report, we congnized that the time of giving Singulair to patient shouldne in paracmasis of asthma. It is not refer to acute asthmatic attack. Application ofdrug need to electing not only suitable dose, but also perfect time. Organism haspersonal adjusted in allergy, incorrect interference may be to break certainequilibrium mechanism, caused sickness development to severity.The point of bring new ideas in our experiment is approaching geneticexpress level of IL-12, β2AR and CysLT1-receptor;Preparing the asthma andairway remodeling model of Wistar rat;And intertenting it by drug, contrastingthe effect of intervention;Approaching the Sigulair's different influence to airwayremodeling in different dosage time. This test expounded the dicyto-mechanismabout asthma and airway remodeling;It would offered chances for neotypedrug ,offered the theory for gene therapy for asthma and established a compactrationale for clinical dosage of individuation and normalization.