[The effect of simvastatin on alveolar epithelial cells in cigarette smoking-induced emphysema].

ABSTRACT

OBJECTIVE: to explore the effect of simvastatin on alveolar epithelial cells and the expression of vascular endothelial growth factor (VEGF) in cigarette smoking-induced emphysema in rats. METHODS: twenty-four, 12-week-old healthy male and female Wistar rats were randomly divided into 4 groups of 6 each a control (W) group, a smoking (Sm) group, a simvastatin (St) group, and a smoking-simvastatin (SmSt) group. The rats were simultaneously fed, and kept in individual cages for 16 weeks. The VEGF level in lung tissue and bronchoalveolar lavage fluid (BALF) of each group was measured by ELISA. The expression of VEGF mRNA was determined by RT-PCR. The expressions of VEGF and proliferating cell nuclear antigen (PCNA) were determined by two-step immunohistochemistry assay. One-way ANOVA and LSD-t test were used for statistical analysis. RESULTS: the percentage of PCNA-positively stained alveolar epithelial cells was significantly higher in the SmSt group [(10.3 ± 2.0)%] than in the Sm group [(4.8 ± 0.8)%]. The levels of VEGF in BALF and lung tissue homogenate of the SmSt group [(187 ± 15) ng/L and (6782 ± 50) ng/L] were similar to the W group [(200 ± 20) ng/L and (7558 ± 330) ng/L], but were significantly higher than that in the Sm group [(71 ± 16) ng/L and (4149 ± 110) ng/L]. VEGF expression in alveolar and bronchial epithelial cells of rats in the SmSt group [(67.7 ± 5.0)% and (49.0 ± 3.0)%], was similar to the W group [(68.3 ± 3.3)% and (51.3 ± 2.9)%]. But the level of VEGF expression was significantly increased as compared to that in the Sm group [(27.0 ± 5.9)% and (16.3 ± 2.7)%]. SmSt group vs Sm group t = 1.117 - 12.001, all P < 0.01. CONCLUSIONS: simvastatin ameliorated the development of cigarette smoke-induced COPD in rats, partly by promoting alveolar epithelial cell proliferation and up-regulating the expression of VEGF.