Effects Of Atmospheric PM_2.5 On Histone Acetylation Of Lung Tissue In Asthmatic Rats And Its Mechanism

Objective:To investigate the effects of atmospheric PM_2.5 on histone acetylation and STAT4/STAT6 signaling molecules and cytokines in asthmatic rats.Methods:Forty-five male SD rats were selected to establish a model of PM_2.5-induced asthma model.The rats were randomly divided into 5 groups,saline control group（A）,asthma group（B）,PM_2.5 low,medium,high dose stimulation asthma group（C,D,E）.HDAC1 and HDAC2 mRNA and protein expression levels were detected by qRT-PCR and Western blot,H3K9,H3K18 acetylation level were detemined by quantitative detection kit,immunohistochemical.STAT4 and STAT6 mRNA were detected by qRT-PCR,Western blot was used to determine the relative ptotein expression of p-STAT4 and p-STAT6.IFN-γ,IL-4 and IL-13 were measured by ELISA.Results:The expression of HDAC2 mRNA in group D and group E was lower than that in group B,the difference was statistically significant（P<0.05）.The expression of HDAC1protein in group D was lower than that in group B,and the expression of HDAC2 protein in group E was lower than that in group B（P<0.05）.The acetylation levels of H3K9 in lungs of groups C,D and E were higher than that of group B respectively.The levels of H3K18 acetylation in lungs of group E were higher than those of groups B,C and D（P<0.05）.Immunohistochemistry showed that H3K9ac,H3K18ac protein expression mainly concentrated in bronchial epithelial cells.The both indicators overall group B expression was higher than group A,and D,E group was higher than the B group,the difference was statistically significant.The relative expression of STAT6 mRNA in group B was higher than that in group A,and in group D it was higher than that in group B and C（P<0.05）.The expression of p-STAT6 protein in group B was higher than that in group A,and the levels in group D and E were higher than those in group B and C（P<0.05）.The expression of p-STAT4 protein in group B was higher than that in group A,D and E were higher than those in group B and C,and E group was higher than that in group D.The difference was statistically significant（P<0.05）.The level of IL-4 in lung tissue of group B was higher than that of group A,the level of IL-13 in group D and E was higher than that of group B,and the level of IL-13 in group D and E was higher than that of group B（P<0.05）.The level of HDAC1 protein in lung tissue of rats was significantly negatively correlated with the level of H3K9ac,as the level of HDAC2protein and the level of H3K18ac.The expression level of HDAC1 was negatively correlated with the level of H3K18ac,also the level of HDAC2 protein was negatively correlated with the level of H3K9ac.The protein levels of HDAC1 and HDAC2 were negatively correlated with the level of p-STAT6 protein.The expressions of HDAC1protein was negatively correlated with the levels of p-STAT4 protein.The level of acetylation of H3K9 was positively correlated with the levels of p-STAT6 and negatively with p-STAT4 protein respectively.There was a significant positive correlation between the level of acetylation of H3K18 and the levels of STAT6 mRNA and p-STAT6 protein.The level of acetylation of H3K18 was significantly negatively correlated with the level of p-STAT4 protein.Conclusion:1)Atmospheric PM_2.5 can promote Th2 cytokine secretion in asthmatic rats.2)Atmospheric PM_2.5 increase the acetylation of histone H3K9 and H3K18 by decreasing the expression of HDAC1 and HDAC2,and mediate the expression of transcription factor STAT4/STAT6,which may exacerbated asthma.