Laboratory Study On Airway Inflammation And The Effects Of Drugs In Rats With Chronic Obstructive Pulmonary Diseases

Objective (1) To investigate the character of airway inflammation in chronic obstructive pulmonary disease (COPD). (2) To study the role of cytokine in the chronic airway inflammation of COPD. (3) To observe the protective and therapeutic effects of erythromycin (EM) on airway inflammation of COPD .Methods (1) All rats were randomly divided into several groups: normal group, control group, COPD group (model group), EM treatment groups, EM preventive and treatment groups. The rat models of COPD were established by intratracheal instillation of lipopolysaccharide (LPS) twice and exposure to cigarette smoke daily. EM treatment groups received gastric gavage of EM, starting on the 14th day, and drug preventive treatment groups were given EM 3 days prior to instillation of LPS. (2) At the end of fourth weeks, the levels of interleukin-1 β (IL-1β ), tumor necrosis factor-α (TNF α ), monocyte chemotactic protein-1 (MCP-1) in bronchoalveolar lavage fluids (BALF) or serum were measured by enzyme-linked immunosorbant assays technique (ELISA). (3) Totaland differential cell counts in BALF were done. (4)Tissue was fixed by inflating with formalin from right lung. Sagittal sections were stained with hematoxylin-eosin or masson , and the pathomorphological changes were analysed.Results (1) The COPD group rats shared specific pathological features in trachea, bronchi and lung tissues with that of human chronic bronchitis and emphysema. Significant increase in thickening of the smooth muscles and collagen was found in COPD group (P<0.05) than that of control group. The pathologic integral of airway inflammation was also significantly increased in COPD group than that in control group. The numbers of total white cell counts , neutrophils and alveolar monocyte-macrophage in BALF obtained from COPD group were higher than those in control group (P0.05). The levels of IL-1β ,TNF-α ,MCP-1 in BALF or serum were increased in COPD group (P<0.05) than those in control group. (2) Compared with the COPD group, the number of total cell counts from BALF in EM treatment group were decreased , but it was not statistical significance. The numbers of neutrophils from BALF, the levels of TNF- α in serum were also significantly decreased(P<0.05),whereas MCP-1 were significantly increased(P>0.05) after EM treatment. In preventive and treatment groups, the numbers of neutrophils in BALF, the levels of TNF- a in serum or BALF , IL-1 β in serum were also significantly decreased(P<0.05), but MCP-1 in serum or BALF were significantly increased(P>0.05). Conclusion The infiltration of inflammatory cells ,IL-1β , TNF-α , and MCP-1 might play important roles in the airway inflammation of COPD. EM might partly prevent the development of airway inflammation in COPD by inhibiting the neutrophils accumulation in the lung and reducing the release of IL-1β , TNF- α . The effects of EM were positively correlated with its dose and time of applicationt.