Role Of Connective Tissue Growth Factor In The Pathogenesis Of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive, on which the fibrosis of bronchus, bronchiole and interstitium may play an important role. COPD is a major cause of chronic morbidity and mortality throughout the world. It is important to investigate the pathogenesis of COPD for prevention and treatment of this disease. Connective tissue growth factor (CTGF) is a member of the recently described CCN gene family, which can promote cell proliferation and extracellular matrix deposition. There is evidence that CTGF may be involved in the pathogenesis of various fibrotic disease. This study is to explore the change of CTGF expression in rat COPD model, and to determine the effect of CTGF on the pathogenesis of COPD.Part 1. Establishing rat chronic obstructive pulmonary disease model and pathomorphological analysisObjective: To establish rat chronic obstructive pulmonary disease (COPD) model and analyze the model pathomorphologically,, to investigate the pathomorphology evolution and collagen deposition in rat COPD model. Methods: The rat COPD model(model group) was established by passive smoking and intratracheal instillation of lipopolysaccharide (LPS).According to the days of smoking,fifty rats were random divided to 0 day(control group),7 day,14 day,21 day and 28 day group respectively. The distribution and the ratio of type â…  to type â…¢ collagen in the lung tissue were determined using a Sirius red-polarizing microscopy morphometry method. With semi-quantitative analysis, destructive index (DI) and mean linear intercept (Lm) of COPD rat lung tissue was evaluated. Results: Model group collagen deposition increased and predominant type â…  collagen presented in 21 day and 28 day group (P<0.01).Compared to control group, DI increased significantly in 14 day group, 21 day group and 28 day group(P<0.05). Lm increased significantly in 21 day group and 28 day group (P<0.05). The alteration of DI prior to that of Lm. Conclusions: COPD rat models were successfully established by passive cigarette smoking plus intratracheal instillation of LPS. The results suggested that COPD developed with airway remodeling and alveoli destroy was earlier than alveoli lumen augment.