The Gene Expression Profile Of Asthmatic Rat And The Intervention Study Of Arsenic Trioxide

ObjectivesTo unravel the differential genes expression during asthmatic rats modelsestablishment and to assess the effect of arsenic trioxide on the differential genesexpression during asthma occurrence in rat.MethodsSeventy healthy male clean SD rats were randomly divided into three groupsat random:10for group A as normal control group,30for group B as asthma modelgroup (two weeks as group B1; four weeks as groupB2; eight weeks as group B3, n=10),30for group C as arsenic trioxide intervention group (two weeks as group C1;four weeks as group C2; eight weeks as group C3). Intraperitoneal injection ofinhalation ovalbumin asthma model and bronchoalveolar lavage fluid of rats weresacrificed24h after the last challenge and the number of white blood cells andeosinophils were counted in bronchoalveolar lavage fluid (BALF). The left lung wasstained with HE, and analyzed with pathological image. Total RNA was extractedfrom right lung extraction for gene differential expression microarray, and2folds ofgene expression changes was defined as targeted altered gene. GO and Pathwayanalysis were utilized for functional classification analysis of obtained differentialgenes and real-time quantitative PCR was used for the validation of microarrayresults.Results1.the total number of white blood cells and the proportion of eosinophils (EOS)in the BALF showed an increase in asthmatic model group, compared with those innormal group (P <0.05), and those data presented a obvious decrease in arsenictrioxide group,compared to those in the asthma model group (P <0.05).2. Inflammatory cell infiltration including eosinophils and lymphocytes was found in rat airway bronchial of asthma model rats. Perivascular airway smoothmuscle and basement membrane were found to be thickened, astenosis was observedand sub mucosal deposition of extracellular matrix was increased in asthma modelrats. Those symptoms were improved by the use of arsenic trioxide in asthma modelrats.3. Total438differentially expressed genes were obtained when asthma modelgroup was compared to normal group in a24,358genes microarray, of which348were up-regulated and90were down-regulated in asthma model group. Total236differentially expressed genes were observed when arsenic trioxide group wascompared with asthma model group, of which96were up-regulated and140down-regulated in arsenic trioxide group. GZMA and MAL showed decreased expression inasthma model rats and arsenic trioxide intervention revered the process in genesmicroarray, which was further confirmed by real-time quantitative PCR.Conclusions1. GZMA and MAL might be involved in the progression of asthma.2. Arsenic trioxide could improve asthma by enhancing the expression ofGZMA and MAL in the lung tissue.