The Role Of MiR155/miR146a/miR31 And STAT6/NF-κB/FOXP3 In Asthma Exacerbation Of Rats Induced By PM_2.5

Objective:To investigate whether PM_2.5 could change the expression of miR155,miR146 a,miR31 and the transcription factors of STAT6,NF-κB,FOXP3 in asthmatic rats,and the level of IL-13,IL-8,IL-10,and to provide a scientific basis for the pathogenesis of PM_2.5 aggravating asthma.Methods:A total of 45 SD rats were randomly assigned into 5 groups,including the normal saline control group,the asthma group,the asthma+ PM_2.5 low dose group,the asthma+ PM_2.5 medium dose group and the asthma+ PM_2.5 high dose group.Asthma model was reproduced by sensitization with intraperitoneal injection and inhalation of ovalbumin（OVA）.On day 25,28,31 and 34,the rats were administrated with PM_2.5 by intratracheal instillation.The rats were sacrificed on day 36,the bronchoalveolar lavage fluid（BALF）was collected and the number of the cells in BALF was counted.The changes of weight and organ coefficient of rats were analyzed.We observed the pathological changes and inflammatory cell infiltration by hematoxylin-eosin（HE）staining of lung tissues of rats.The expression of miR155,miR146 a,miR31 and the gene expression of STAT6,NF-κB,FOXP3,IL-13,IL-10 in rat lung tissues were detected by RT-PCR.The protein expression of p-STAT6,NF-κB and FOXP3 in rat lung tissue were detected by Western-blot.The level of IL-13 and IL-10 in BALF were detected by ELISA.And the correlation among miRNA,nuclear transcription factor and cytokines were analyzed.Results:1.The percentage of eosinophil,neutrophil and lymphocyte,left lung organ coefficient and the total cell count in the asthma group were higher than those in the control group,the percentage of eosinophil,neutrophil and lymphocyte in asthma+ PM_2.5 low,medium and high dose groups were higher than the asthma groups（P<0.05）.2.The expression of miR146 a in asthma group was higher than that in control group,the expression of miR155,NF-κB gene and IL-8 level of BALF in asthma+PM_2.5 medium and high dose groups and the expression of miR146 a and STAT6 gene in asthma+PM_2.5 high dose group were higher than that the asthma group,the expression of miR155,STAT6 gene and the IL-8 level of BALF were higher than that in the asthma+PM_2.5 low dose group（P<0.05）.3.The gene and protein expression of FOXP3 and gene expression of IL-10 in asthma group were lower than control group,the expression of the miR31 and the gene and protein expression of FOXP3 in asthma+PM_2.5 medium and high dose groups were lower than that asthma group,the protein expression of FOXP3 in asthma+PM_2.5 high dose group was lower than that in the asthma+PM_2.5 low dose group（P<0.05）.4.The expression of miR155 in rat lung tissue was correlated with the gene and protein expression of STAT6 and IL-13,the expression of miR146 a in rat lung tissue was correlated with the protein expression of NF-κB and IL-8,the expression of miR31 in rat lung tissue was correlated with the gene and protein expression of FOXP3 and IL-10（P<0.05）.Conclusion:PM_2.5 could change the expression of miR155,miR146 a,miR31 and the transcription factors of STAT6,NF-κB,FOXP3 in asthmatic rats,and affect the level of IL-13,IL-8,IL-10 in BALF,and thus could induce the asthma exacerbation.