〔Abstract〕 Objective To investigate the effect and possible mechanism of microRNA-181 a(miR-181 a) on airway remodeling in the lung tissue of rats with chronic obstructive pulmonary disease(COPD).Methods Sixty-five rats were randomly selected from 80 rats to establish COPD models, 56 rats were successfully modeled.They were randomly divided into model group, NC group, mimics group and inhibitors group with 14 rats in each group, and the remaining 15 rats were sham operation group.Two hours after modeling, the mimics group, the inhibitors group and the NC group were injected with miR-181 a mimics, miR-181 a inhibitors and control mimics through the tail vein, and the sham operation group and the model group were injected with saline.After 24 hours of intervention, RT-qPCR was used to detect the relative expression levels of miR-181 a and maternal signal protein homolog 7(Smad7) mRNA in lung tissue, ELISA method was used to detect the levels of interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in lung tissue homogenate, luciferase reporter gene analysis miR-181 a targeting Smad7,HE staining to observe rat lung tissue disease physiological changes, measure bronchial wall and bronchial wall collagen fiber thickness, Western blot was used to detecte lung tissue matrix metalloproteinase-9(MMP-9),transforming growth factor β1(TGF-β1),Smad7,p-Smad7 protein relative expression level. Results Compared with the sham operation group, the relative expression level of miR-181 a in lung tissues of the model group, NC group and inhibitors group decreased, and the relative expression level of miR-181 a in lung tissue of the mimics group increased, and the mimics group>model group and NC group>inhibitors group(P<0.05).Compared with the sham operation group, the levels of IL-1β and TNF-α in lung tissue homogenate of the model group, NC group, mimics group, and inhibitors group increased, and the inhibitors group>model group and NC group>mimics group(P<0.05).The results of the dual luciferase reporter gene analysis system showed that miR-181 a could significantly inhibit the relative luciferase activity of wild-type Smad7(P<0.05),but had no significant effect on the relative luciferase activity of mutant Smad7(P>0.05).HE staining showed that the alveolar cells of the rats in the sham operation group were normal, and the lung parenchyma of the rats in the model group, NC group and inhibitors group was destroyed, with inflammatory cell infiltration and collagen fiber formation.In the mimics group, alveolar cells tended to be normal, inflammation reduced, collagen fibers decreased, and alveolar structural disorder was significantly improved.Compared with the sham operation group,the bronchial wall and bronchial wall collagen fibers in the model group,NC group,mimics group,and inhibitors group were thickened,and the inhibitors group>model group and NC group>mimics group( P<0. 05). Compared with the sham operation group,the relative expression levels of MMP-9 and TGF-β1 protein in the lung tissues of the model group,NC group,mimics group and inhibitors group increased,while the relative expression level of p-Smad7 protein decreased,and MMP-9,TGF-β1 protein relative expression level inhibitors group>model group and NC group>mimics group,relative expression of p-Smad7 protein mimics group>model group and NC group>inhibitors group( P<0. 05). Comparison of the relative expression levels of miR-181 a,IL-1β,TNF-α levels,bronchial wall and bronchial wall collagen fiber thickness,MMP-9,p-Smad7,and TGF-β1 protein expression levels in the model group and NC group,there was no statistical significance( P>0. 05). Conclusion miR-181 a can improve the airway remodeling in the lung tissue of COPD model rats,and may play a role in the targeted regulation of Smad7 expression.