Inhibition Of Melatonin On Airway Oxidative Stress And Lung Inflammation In Rats With Chronic Obstructive Pulmonary Disease

Objective: Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible. The pathogenesis of COPD is complex and it is difficult to treat. To investigate the effect of melatonin (MLT) on lung inflammation and airway oxidative stress in rats with COPD, we could find the theoretical evidence to prevent and manage COPD by MLT.Methods: 36 male wistar rats were randomly divided into 3 groups as follows: control group, COPD group and MLT group. The COPD model was established by intratracheal lipopolysaccharide (LPS) and exposure to cigarette smoking for 28 days, the MLT group was given intraperitoneal injection of 10 mg/kg MLT 30 minutes before each cigarette challenge. After incision of trachea, the lung function was measured. Then the rats were lavaged, the total and different white blood cell counts of bronchial alveolar lavage fluid (BALF) were determined, nitric oxide (NO), malondialdehyde(MDA), total superoxide dismutase(T-SOD), glutathione superoxide (GSH-PX) in BALF were carry out respectively. Then, after the lung homogenates were obtained, we analyzed the content of myeloperoxidase (MPO), tumor necrosis factor (TNF-α), interleukin -8(IL-8) in BALF and homogenates. The pathological changes were observed with light microscope.Results :(1) Significant decrease in total white blood cells and neutrophils in BALF was found in MLT group than these in COPD group (P<0.01, P<0.05, respectively), and the ratio of monocyt-macrophage was lower in MLT group. (2) NO and MDA in BALF of MLT group significantly decreased (P<0.05), T-SOD and GSH-PX in BALF of MLT group significantly increased (P<0.05), compared with those of COPD group. (3)The content of MPO, TNF-α, IL-8 in BALF and lung homogenates of MLT group remarkably decreased compared with those of COPD group (P<0.01 or P<0.05). (4) Forced expiratory volume in 0.3 second (FEV0.3), forced expiratory volume in 0.3 second /forced vital capacity (FEV0.3/FVC) and peak expiratory flow (PEF) in MLT group were higher than those in COPD group, but there were no obvious differences between these groups. (5) The model rats shared specific pathological features in bronchial walls and lung tissues, the pathological damages in MLT group were lessened but still abnormal.Conclusions: We successfully replicated the COPD experimental models .Early intervention with MLT can partly inhibit proceeding of COPD by decreasing the cells and mediators of inflammation, airway oxidative stress and increasing activity of antioxidant.