The Study On The Roles Played By NKT Cells In The Pathogenesis Of Obese Asthma

Part 1 Establishment and comparison of obese asthma models in different strains of miceObjective To establish and compare different strains of mice obese asthma models.methods The clean 3-4-week-old weaning female mice from three different mouse strains KM?BALB/c and C57BL/6j were randomly divided into 4 groups.Group A is control group,group B is asthma group,group C is obesity group and group D is obese asthma group.The mice were fed a high-fat or normal diet for 12 weeks and group B and group D subsequently sensitized and challenged with ovalbumin(OVA)or phosphate-buffered saline(PBS).At The end of this study,Body,adipose tissue,and liver weights,Lee's index,OVA-specific IgE levels in bronchoalveolar lavage fluid(BALF),serum total cholesterol(TC)and triglyceride(TG)levels,cross-sectional area of adipocytes and lung and adipose tissue morphology were assessed in all groups.Results:In the obese KM mice,Body,adipose tissue,liver weights and cross-sectional area of adipocytes were significantly increased(P<0.01),and Lee's index and serum total cholesterol(TC)were also increased(P<0.05),while OVA-specific IgE levels in bronchoalveolar lavage fluid(BALF)and histological examination of the lungs showed airway inflammation of group B and group D were no significant difference.In high-fat diet BALB/c mice,Body,adipose tissue,liver weights and Lee's index were significantly increased(P<0.01),cross-sectional area of adipocytes and serum total cholesterol(TC)were also increased(P<0.05).And BALB/c mice in group B and group D demonstrated more significant symptoms of acute asthma,local inflammation and air way remodeling,and OVA-specific IgE levels was significantly increased(P<0.01).When talk about the obese C57BL/6j mice,Body,adipose tissue,liver weights and Lee's index were increased(P<0.05),but cross-sectional area of adipocytes and serum total cholesterol(TC)were increased but without any significance(P>0.05).Although OVA-specific IgE levels was increased(P<0.05)and significant symptoms of acute asthma,local inflammation were demonstrated in asthma mice,air way remodeling was not obvious.Conclusion:In comparison with KM mice and C57BL/6J mice,BALB/C mice which were fed with high-fat diet,sensitized and challenged with ovalbumin(OVA)provide the most suitable tool in the fundamental research of obese asthma.Part 2 The roles of NKT cells function and differentiation in the pathogenesis of obese asthmaObjective:To explore the role of NKT cells and their function in the pathogenesis of obese asthma by observing the airway inflammation,airway reactivity,the number of NKT cells,theIL-4+NKTs cell and IFN-y+cells and the serum levels of cytokines.Methods:The clean 3-4-week-old weaning female mice were randomly divided into 4 groups.Group A is control group,group B is asthma group,group C is obesity group and group D is obese asthma group.Mice were fed with high-fat diet to induce obese model,and were sensitized and challenged with ovalbumin(OVA)to make a asthma model.the specific airway resistance(sRaw)was measured using double-chamber plethysmography.Pathological HE staining made to measure lung imflammation.Flow cytometric analysis for cell surface molecular markers and intracellular cytokines of NKT cells.The serum levels of cytokines were measured as well.Results:Compared to control group,AHR and airway inflammation in group B and group D were increased,especially in group D.lung imflammation was most severe in group D.The concentration of serum IL-4 was mostly increased in group C.The concentration of serum IFN-y was decreased significantly in group B and group D.The percentage of CD1d+NKT cells increased in group Band D,while decreased significantly group C.The percentage of IL-4+NKT cells increased in group B,C and D,and especially in group C.The percentage of IFN-y+NKT cells decreased in group B,C,D.And the percentage of CD69+NKT cells's change did not agree with the percentage of CD69+NKT cells's.Conclusion:The NKT cells play an important role in pathogenesis of obese asthma.Further investigation on NKT cells is useful to prevention and therapy of obese asthma.