Effects Of Tiotropium Bromide On Airway Inflammation And Remodeling In Chronic Obstructive Pulmonary Disease Rat Model

Objectives : To evaluate the effects of tiotropium bromide on the airway inflammation and remodeling in chronic obstructive pulmonary disease( COPD )rats.Methods: All twenty four male Wistar rats were offered by animal experimental center of Shan Xi medical university. Rats were randomly divided into three groups: normal control group, COPD group, tiotropium bromide treated group. The COPD rat model was established by intratracheal instillation of lipopolysaccharide twice and daily exposure to cigarette smoking. Tiotropium bromide treated group received inhalation of tiotropium bromide since the eighth day. All of the rats in three groups were sacrificed to be tested at the end of three months. Total and differential cell counts in right lungs bronchoalveolar lavage fluid (BALF) were observed. Animal right lungs were prepared to stain with hematoxylin and eosin (HE) to assess the inflammatory cell infiltration , masson,s trichrome to determine collagen deposition in the lungs and immunohistochemical analysis to examine matrix metalloprotease-9(MMP-9) protein after fixing with infusion of 4% formalin . The expression of TGF-β1 mRNA was assessed by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).and the pathommorpholigical changes in the lung were analyzed. The following morphmetric parameters with a computerized image analysis system were measured in all airway cuts: thickness of the airway wall, smooth muscles and collagen in the bronchial wall. All data were analyzed by statistical software SPSS 13.0. Values of P<0.05 were regarded as significant.Results:1 By light microscopy specimens in normal control group neither airway nor alveolus showed abnormal findings. All cases of model group showed wide inflammatory changes in bronchiole and servere emphysema, which was accorded with those of chronic obstructive pulmonary disease .2 Compare with normal control group the numbers of total white cell counts and neutrophils in BALF of COPD group and tiotropium bromide treated group increased(P<0.01).3 Morphmetric Analysis of the Airway: The thickness of each category airway wall and collagen in COPD group were significantly greater than in normal control group (P<0.01),which were limited by tiotropium bromide intervention (P<0.05)4 The expression of TGF-β1 mRNA and MMP-9 protein significantly increased in bronchi and lung tissue of COPD group as Compare with those of normal control group (P<0.01), and which in tiotropium bromide treated group was significantly decreased than in COPD group (P<0.05).Conclusions:1 It is a useful tool to study COPD airway inflammation and remodeling with the model of three months smoking plus twice intratracheal instillation of lipopolysaccharide .2 TGF-β1 and MMP-9 may play an important role in the airway inflammation and remodeling process of COPD . To study the modulation net of TGF-β1 and MMP-9 may be helpful to investigate the pathogenesis of COPD.3 Tiotropium bromide could somewhat inhibit the airway inflammation and remodeling process of COPD by influence the expression of TGF-β1 mRNA and MMP-9 protein.