The Effect Of Simvastatin On Inflammation In Chronic Obstructive Pulmonary Diseases Rat Model

[Objective] To observe the effect of Simvastatin on inflammatory factors and lung pathology of chronic obstructive pulmonary disease rat model. And to investigate the therapeutic action of Simvastatin on COPD, in order to find the theoretical basement for the Simvastatin treatment in COPD[Methods]1. The COPD rat model was established by intratracheal instillation of lipopolysaccharide twice and exposure to cigarette smoking daily.30 male Wistar rats were randomly divided into three groups:normal control group, COPD model group, Simvastatin treated group.The Simvastatin treated group was treated with Simvastatin by 2.5mg/kg daily from the end of second week for 6 weeks.2. To observe the general condition and weight growth of each group, total and differential cell counts in bronchoalveolar lavage fluid (BALF); and the pathomorphological changes in the lung were analyzed. To observe the IL-8,TNF-αlevels in BALF and serum, CRP level in serum.[Results]1. Observe the general conditions include coat, activity, diet, cough and body mass growth rate in each group.Compared with model group, general conditions improved in Simvastatin treated group, body mass growth rate increased significantly (P<0.01).2. Pathological changes in each groupThe normal control group shows that the ciliated columnar epithelial cells of tracheal mucosa integrity, and cilia arranged neatly, there is little goblet cells in all levels of bronchi, little inflammatory cells infiltrated and the airway structure is nomal.There is no inflammatory cell infiltrated in peripheral vascular wall, the size of alveolar is normal and structural is integrity, with little inflammatory cell infiltrated in.We can find the formation of emphysema in COPD model group, epithelial cilia lodged in trachea and bronchial,some epithelial shedding and goblet cell hyperplasia,.There are much inflammatory cells infiltrated in submucosal and muscular layers, some acinar atrophy, much inflammatory cell infiltrate around vascular and capillary hyperemia.The alveolar structure is incomplete, alveolar wall become thin and fracture, much inflammatory cells infiltrate in alveolar septum.We alse can see emphysema in simvastatin treated group, but the levels are abated in airway epithelial cells shedding, goblet cells increased and inflammatory cells infiltration around trachea and blood vessels.3. Total number cells and classification of BALFTotal number cells and the proportion of neutrophils, monocytes-macrophages and lymphocytes were significantly different in the three groups (P<0.01); compared with the normal control group, the total cell and neutrophil percentage was significantly increased in COPD model group and Simvastatin treated group (P <0.05); compared with the COPD model group, the total cell and neutrophil percentage was significantly decreased in Simvastatin treated group (P<0.01).4. The level of IL-8 and TNF-αin BALFThe level of IL-8 and TNF-αin BALF were significantly different in the three groups (P<0.01); compared with the normal control group, the level of IL-8 and TNF-αin BALF was significantly increased in COPD model group and Simvastatin treated group (P<0.01); compared with the COPD model group, the level of IL-8 and TNF-αin BALF was decreased significantly in Simvastatin treated group (P<0.01).5. The level of IL-8,TNF-αand CRP in serumThe level of IL-8,TNF-αand CRP in serum were significantly different in the three groups (P<0.01); compared with the normal control group, the level of IL-8,TNF-αand CRP in serum was significantly increased in COPD model group and Simvastatin treated group (P<0.01); compared with the COPD model group, the level of IL-8,TNF-αand CRP in serum was decreased significantly in Simvastatin treated group (P<0.05).6. The correlation between the neutrophil proportion of BALF and IL-8 level in each groupThe neutrophil proportion of BALF and IL-8 concentration had no correlation relationship in normal control group (r=0.54, P>0.05), neutrophil proportion of BALF and IL-8 level were significantly correlated in COPD model group (r=0.834, P<0.01, correlation equation y=0.5532x+8.6675), neutrophil proportion of BALF and IL-8 level were significantly correlated in simvastatin treated group (r=0.799, P<0.01, correlation equation y=0.3859x+10.595).7. The correlation between the neutrophil proportion of BALF and TNF-a level in each groupThe neutrophil proportion of BALF and TNF-a level had no correlation relationship in normal control group (r= 0.337, P>0.05), neutrophil proportion of BALF and TNF-a level had no correlation relationship in COPD model group (r=0.300, P>0.05), neutrophil proportion of BALF and TNF-a level had no correlation relationship in simvastatin treated group (r=0.561,P>0.05).【Conclusion】1. Simvastatin can improve the general situation in COPD rat model and increase the body mass growth rate.2. Simvastatin can reduce the infiltration of inflammatory cell around the bronchial and pulmonary vascular airway inflammation in COPD rat model.3. Simvastatin can reduce airway inflammation and systemic inflammatory response of COPD rat model, is expected to provide a new drug choice for COPD treatment.