动物造模,慢阻肺 z-bio 2022-10-13 522

　　Objective To investigate the effect of metformin (Met)-regulated microRNA (miR)-34a on airway inflammation in rats with chronic obstructive pulmonary disease (COPD).

　　Methods The COPD rat model was prepared by instilling 2 mL of lipopolysaccharide (LPS) solution through the airway on the 1st, 14th, and 28th days by smoking for 30 min every day. Met was detected by real-time quantitative PCR (qRT-PCR). The effect on the level of miR-34a in lung tissue; the white blood cell count in bronchoalveolar lavage fluid (BALF) and the wright staining classification to detect the effect of Met; the effect of Met on lung tissue morphology detected by hematoxylin-eosin (HE); enzyme The effect of Met on the levels of interleukins IL-6, IL-8, IL-1β and tumor necrosis factor-α (TNF-α) in serum was detected by ELISA; the level of sirt1 protein in lung tissue was detected by Western blot. TargetScan finds the 3′UTR of sirt1 mRNA and the binding site of miR-34a, and is identified by the dual-luciferase reporter gene detection kit.

　　Results Compared with the control group, the level of sirt1 protein, the ratio of monocytes and macrophages in the lung tissue of the model group decreased (P<0.05), the level of miR-34a, the number of leukocytes in BALF, neutrophils, eosinophils The ratio of cells to lymphocytes, serum IL-6, IL-8, IL-1β, and TNF-α levels increased (P<0.05); adding Met could alleviate the sirt1 protein level in lung tissue, and the monocyte-megaloblastic The proportion of phagocytes decreased, the level of miR-34a, the number of leukocytes in BALF, the proportion of neutrophils, eosinophils and lymphocytes, and the levels of IL-6, IL-8, IL-1β and TNF-α in serum increased (P<0.05); Elevating the level of miR-34a reversed the effect of Met on COPD rats. And verified by dual luciferase, there is a targeting relationship between miR-34a and sirt1.

　　Conclusion Met can down-regulate miR-34a and then up-regulate sirt1 to relieve airway inflammation in COPD, which provides a certain experimental basis and basis for clinical treatment of COPD with Met.