Simvastatin promotes alveolar epithelial cell proliferation and attenuates cigarette smoke-induced emphysema in rats

Current treatments for chronic obstructive pulmonary disease (COPD) cannot reverse the pathological process of the disease, therefore, the development of novel agents and strategies for COPD treatment is required. The aim of the present study was to investigate the potential therapeutic value of simvastatin (SmSt) in cigarette smoke-induced emphysema in rats. A total of 24 male and female Wistar rats were randomly divided into four groups. The levels of vascular endothelial growth factor (VEGF) in the lung tissues and bronchoalveolar lavage (BAL) fluid of each group were measured using an enzyme-linked immunoassay. The mRNA expression of VEGF was assessed using reverse transcription-quantitative polymerase chain reaction. The protein expression levels of VEGF and proliferating cell nuclear antigen (PCNA) were determined using immunohistochemical assays. Histological scoring revealed that simvastatin reduced the total inflammatory scores significantly more in the simvastatin-treated. smoke-exposed group, compared with the smoke exposed (Sm) group. Significant differences in the average inter-alveolar septal wall distance and mean alveolar numbers were also observed between the SmSt and Sm groups. The levels of VEGF in the BAL fluid and lung tissue homogenates of the SmSt group were similar to those in the simvostatin-only (St) and control (CtL) groups, and significantly higher compared with those in the Sm group. The expression of VEGF in the alveolar and bronchial epithelial cells of the SmSt group was similar to that in the CtL group, and significantly higher compared with that of the Sm group. The percentage of PCNA-positive alveolar epithelial cells was significantly higher in the SmSt group compared with the Sm and CtL groups. Simvastatin exerted a significant impact on the expression of VEGF and attenuated cigarette smoke-induced emphysema in rats. Therefore simvastatin may have beneficial effects in patients with COPD.