Changes Of MiR-155 In Lung Tissue Of Bronchialasthma Mice And The Effects Of Curcumin

Background: Asthma is an allergic disease with abnormal immune function.Currently,inhaled corticosteroids and bronchodilators are the most effective treatments for asthma,but not for all patients.microRNA-155(miR-155)is a class of endogenous,non-coding,single-stranded RNAs that are highly expressed in activated B cells,T cells,dendritic cells,and macrophages.is highly expressed in activated B cells,T cells,dendritic cells,and macrophages,and is essential for cellular functions of innate and/or adaptive immune responses,and is closely related to airway inflammation in asthma,regulate the development of asthma through genetic levels.Remodeling of the respiratory tract is a key feature of chronic asthma.Studies have shown that the expression of Cyclooxygenase-2(COX-2)and miR-155 is increased in Airway smooth muscle(ASM)cells of asthmatic patients,and COX-2/ Phenyl glycidyl ether 2(PGE2)is involved in the cellular response that drives remodeling.Curcumin,an antioxidant polyphenol from turmeric,is the main component of curry spice turmeric,and it has chemoprevention,anti-proliferation,pro-apoptosis,anti-metastasis,anti-angiogenesis and anti-inflammatory effects,it has been found to be an anti-inflammatory molecule with strong anti-asthma potential,which can effectively alleviate airway obstruction,airway hyperresponsiveness,inflammatory cell infiltration and other symptoms of asthmatic model and Th2 cytokines Abnormally high expression and so on.The p38Mitogen-activated protein kinase(p38MAPK)signaling pathway plays a crucial role in the inflammatory action of asthma by mediating apoptosis,promoting the synthesis of various cytokines and recruiting inflammatory cells.Objective: In this study,the mouse model of bronchial asthma was replicated to investigate the changes of miR-155 and COX-2 in lung tissue of bronchial asthmatic mice.At the same time,to investigate the effect of curcumin on the expression of miR-155 and COX-2 in lung tissue of bronchial asthma mice.Methods: Forty-two female BALB/c mice were randomly divided into seven groups(n=7 each): control group,asthmatic group,low dose group of curcumin,high dose group of curcumin,antagomir negative control group and antagomir-155 intervention group.The bronchial asthma model was induced by intraperitoneal injection of chicken egg ovalbumin(OVA)and repeated ultrasonic atomizationinhalation,and observed the asthmatic performance of each group of mice.The concentration of PGE2 in peripheral blood of mice,the expression of Phosphorylated p38 MAPK(P-p38MAPK),COX-2 protein,COX-2 m RNA and miR-155-5p m RNA in lung tissue were detected by Enzyme linked immunosorbent assay(ELISA)kit,Western Blotting and reverse transcription PCR(RT-PCR),respectively,the lung inflammation infiltration was observed by HE staining.Results: The expressions of miR-155-5p,COX-2 m RNA,COX-2 protein and serum PGE2 in lung tissue of the asthmatic group and the antagomir negative control group were significantly higher than control group and antagomir-155 intervention group(P<0.01).The phosphorylation of p38 MAPK in lung tissue of the asthmatic group and the antagomir negative control group was significantly higher than that of normal control group and antagomir-155 intervention group(P<0.01;P<0.05).The expression of miR-155-5p,COX-2 and serum PGE2 in the lung tissue of the curcumin group was significantly lower than that in the asthmatic group(P<0.01),and there was a statistically significant difference between the low and high doses(P<0.01;P<0.05).The relative expression of phosphorylated p38 protein kinase in curcumin high-dose group was lower than that in model group(P<0.05)and there was no significant difference between the low and high doses(P>0.05).The expression of miR-155-5p is significantly positively correlated with COX-2m RNA in the lung(r=0.977,P<0.01).The expression of miR-155-5p is significantly positively correlated with phosphorylated p38 MAPK in the lung(r=0.877,P<0.01).The expression of COX-2 protein in the lung is significantly positively correlated with serum PGE2(r=0.977,P<0.01).The expression of COX-2 protein is significantly positively correlated with phosphorylated p38 MAPK in the lung(r=0.893,P<0.01).In the group of curcumin,the airway wall and airway smooth muscle thickening were not obvious,and a small amount of inflammatory cells infiltrated around the bronchial wall and the blood vessel wall;the antagomir-155 intervention group had less inflammatory cell infiltration than the asthmatic group.Conclusion:The expression of miR-155-5p is increased in lung tissue of bronchial asthmatic mice,and it may be involved in the pathogenesis of asthma by regulating the COX-2/PGE2 pathway or phosphorylating the p38 protein kinasepathway.Curcumin has a therapeutic effect on bronchial asthma,and its mechanism may be related to miR-155-5p,COX-2/PGE2 or phosphorylated P38 protein kinase pathway.