miR-22-3p 通过激活 PTEN/PI3K/AKT/NF-кB 信号通路 加重慢性阻塞性肺疾病.

Objective: To explore the effect and mechanism of mi R-22-3p on chronic obstructive pulmonary disease (COPD).Methods: Male SD rats aged 7 weeks (weight 250 g to 280 g) were randomly divided into 5 groups (n=12): Control group (Con), COPD group, COPD+NC-agomir group, COPD+mi R-22-3p-agomir group, COPD+NC-antagomir group and COPD+mi R-22-3p-antagomir group. The rats in the Con group were normally fed, and the other groups were induced by cigarette smoke (CS) and lipopolysaccharide (LPS). On the day of CS exposure, 50 μL saline was injected intranasally in Con group and COPD group rats. And the rats in COPD+NC agomir group, COPD+mi R-22-3p-agomir group, COPD+NC antagomir group and COPD+mi R-22-3p-antagomir group were given intranasal injection of 50 μL 10 nmol of NC agomir, mi R-22-3p-agomir, NC antagomir and mi R-22-3p-antagomir, respectively. It was injected once every 2 weeks for a total of 6 times. After 90 days of CS exposure, the maximum autonomous ventilation volume per minute (MVV), 0.3 s forced expiratory volume (FEV0.3), forced vital capacity (FVC) and peak expiratory flow (PEF) were measured. The levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid (BALF) were measured by ELISA method. Lung tissue injury was evaluated by hematoxylin-eosin (HE) staining. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in lung tissue were measured according to the instructions of the kit. The m RNA levels of mi R-22-3p, phosphatase and tensin homologue (PTEN), inducible nitric oxide synthase (i NOS), CD86, CD206 and argininase 1 (ARG1) in lung tissue were measured by RT-PCR. The protein levels of PTEN, phosphatidylinositol 3-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, nuclear factor-kappa B (NF-κB) p65 and p-NF-κB p65 in lung tissue were detected by Western blot. Results: Compared with COPD group and COPD+NC-antagomir group, the MVV, FEV0.3/FVC and PEF of COPD+mi R-22-3p-antagomir group increased (P＜0.05), alveolar hemorrhage, rupture of alveolar wall, edema of alveolar septum and inflammatory cell infiltration were alleviated, the levels of IL-1β, TNF-α and MIP-2 in BALF decreased (P＜0.05), the level of SOD in lung tissue increased and the level of MDA decreased (P＜0.05), the relative expression of i NOS and CD86 m RNA in lung tissue decreased (P＜0.05), while the relative expression of CD206 and ARG1mRNA increased (P＜0.05), the relative expression levels of mi R-22-3p in lung tissues decreased, while the relative expression levels of PTEN m RNA and protein increased (P＜0.05), the relative expression of p-PI3K/PI3K, p-AKT/AKT and p-NF-κB p65/NF-κB p65 decreased in lung tissue (P＜0.05). Conclusion: mi R-22-3p is up-regulated in the lung tissues of COPD rats, which may promotes the inflammation and oxidative stress in the lung and aggravates lung dysfunction and lung injury through activating PTEN/PI3K/AKT/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]