The Early Interventional Effect Of Simvastatin In COPD Rats Model

Objective:To explore the possible mechanisms of simvastatin in the treatment of COPD through monitoring and observing the level of IL-6 (Interleukin-6), TNF-a (Tumor necrosis factor-alpha) in the serum, white blood cell count in the BALF (Bronchoalveolar lavage fluid), the expression of MMP-9 (Matrix metalloproteinases-9) in the lung tissue, and the differences of path physiological changes of lung tissue in the COPD rats model. Method: The method of inhaling cigarette smoke and two times of intratracheal instillation of LPS to replicate COPD rat models is adopted.42 rats (Wistar, clean level) were divided randomly into Blank Group, Model Group and Simvastatin Group (14 rats in each group). Lavage treatment with simvastatin (5mg/kg) was giving in Simvastatin Group after 2 weeks when COPD model was established. Usual manifestations and weight changes of rats were observing and monitored in the three groups. The method of biotin double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used in determining IL-6 and TNF-a level in serum and BALF. Result:1. Generally characteristics The rats in Blank Group had generally characteristics of excellent spirit, good appetite and quick response. Their hairs were white, smooth, soft and glossy. However the rats in Model Group showed depression, slow response, lazy to move, eating less but drinking more. Theirs hair were messy, moist, and lacklustre.2. Weight changes There was no significant difference of the weights of rats among the three groups before the experiment (p> 0.05). The weights changes of the rats in Model Group and Simvastatin Group were reduced significantly compared with those in Blank Group after the experiment. (p<0.01).In spite of slightly increase of weight in Simvastatin Group, there was still no statistically significant difference between Simvastatin Group and Model Group (p>0.05).3. Serum levels of IL-6 and TNF-a Blood serum levels of IL-6 and TNF-a of the rats in Model Group were increased significantly than Blank Group (p< 0.05). Compared with Model Group, the serum levels of IL-6 and TNF-a of the rats were obviously lower in Simvastatin Group (p< 0.05).4. BLAF levels of IL-6 and TNF alpha BLAF levels of IL-6 and TNF alpha detected in all rats of Model Group and Simvastatin Group were increased compared with those in Blank Group. (p< 0.01). Otherwise BLAF levels of IL-6 and TNF alpha in rats of Simvastatin Group were significantly lower than that in the model group (p< 0.05).5. WBC count White blood cell count in BALF of the rats in Model Group increased remarkably than those in Blank Group (p< 0.01) but decreasing significantly after simvastatin treatment (p< 0.05).6. MMP-9 expression in lung tissue The expression level of MMP-9 in lung tissue of the rats in Model Group was obviously increased than those in Blank Group(p<0.01). The index was observed somewhat decreased in the rats of Model Group than those of Simvastatin Group.7. Pathological manifestation Cilium adhesion, lodging, defulvium, goblet cell hyperplasia, hyperplasia and hypertrophy of the smooth muscle and chronic inflammation change with a large number of inflammatory cells invasion can be seen at all segments of trachea and bronchi in the rats of Model Group, as well as thinner alveolar walls, which were dilated, ruptured and fused. Pulmonary bullae and emphysema were formed at the same time. Alveolar septum became thickened and alveolar count per unit area was decreased (p<0.01). Bronchioles which accompanied by pulmonary arteritis, intima thickening, tunica media smooth muscle hyperplasia, luminal stenosis and occlusion, and the number of the pulmonary capillaries reduced were coincided with the pathologic characteristics of COPD. The phenomenon of cilia desquamating was reduced in the rats of Simvastatin Group with the alleviated inflammatory infiltration and smooth muscle hyperplasia. The rupture and fusion of alveolae were decreased in this group, which the phenomenon of incrassation of alveolar septum slightly eased and the alveolar number of per unit area increased (p< 0.05). We can also notice in Simvastatin Group that arteritis was alleviated and the capillary lumen occlusion and the reduction of capillary lumen were mildly eased simultaneously. Discussion:1. Pathological manifestation caused by smoke stimulation and airway instillation of LPS are consistent with features of chronic obstructive pulmonary disease, leading to the success of COPD rat model replication.2. Cigarettes inhalation combined with respiratory infections can increase the incidence of lung and systemic inflammation, and induced the over-expression of proteases, getting involved in the emergence and deterioration of COPD.3. Simvastatin therapy as an early intervention can relieve the injury in lung tissue and alleviate tissue remodeling to a certain degree, which may have the mechanism of reducing pulmonary and systemic inflammation and anti protease function.