Simvastatin for lung fibroblast function and its inhibitory pathway in rats

Jicheng XI; Qingyu WU; Lianfeng CHEN

ABSTRACT

BACKGROUND:

Statins can block many intracellular signal transductive pathways and suppress the proliferation of various cells by affecting the synthesis of mevalonic acid and the translation following modification of some membrane-connecting proteins.OBJETCIVE To investigate the influence of simvastatin on the proliferation of lung fibroblasts, the synthesis of collagen and the secretion of matrix metalproteinase-2 (MMP-2).

DESIGN:

Completely randomized controlled study.

SETTING:

At Organ Transplanting Research Institute of Fuwai Cardiovasular Diseases Hospital, Peking Union Medical College.MATERIALS This study was carried out at the Laboratory of Cardiology of Beijing Union Medical College hospital, Peking Union Medical College from June 2004 to October 2004. Lung fibroblasts derived from neonatal SD rats were co-cultured in vitro with different dosage of simvastatin of 0, 1, 5, 10,50 μmol/L, and 50 μmol/L simvastatin + 200 μmol/L mevalonic acid.

METHODS:

Lung fibroblasts deriving from neonatal SD rat were co-cultured with different dosage of simvastatine in vitro. Methyl thiazolyl tetrazolium colorinetry was used to detect the cell proliferation, and cell immunohistochemical assay was used to determine the collagen synthesis and meanwhile,MMP-2 content in supernatant was examined with enzyme-linked immunosorbent assay.MAIN OUTCOME

MEASURES:

The proliferation of fibroblasts, the synthesis of collagen and the secretion of MMP-2 due to different dosage of simvastatin intervention and simvastatin combined with mevalonic acid.presenting the expression of type Ⅰ, Ⅲ of collagen in lung fibroblasts and the level of MMP-2 in 5, 10, 50 μmol/L simvastatin group were obviously lower than those of 0 μmol/L simvastatin group (0. 520 ± 0.010, 0. 334 ± 0.011,0.260±0.012, 0.111±0.011; 0.508±0.011, 0.324±0.014, 0.232±0.015, 0. 083 ±0. 015; 0.445 ±0. 017, 0. 305 ±0. 015, 0.216 ±0. 015,0.068±0.012; 0.561±0.013, 0.361 ±0.012, 0.289±0.012, 0.140value, the mean absorbency( A value) in lung fibroblasts and the level of MMP-2 in 50 μmol/L simvastatin + 200 μmol/L mevalonic acid group were obviously higher than that of the 50 μmol/L simvastatin group(0. 567±0.015, 0.354±0.014, 0.283±0.012, 0.138±0.011, t=4.715-10.950, P ＜ 0.01).

CONCLUSION:

Simvastatin could suppress the fibroblast proliferation and collagen synthesis, attenuate the secretion of MMP-2 and suppress consequently the adhesion and migration of lung fibroblasts; moreover, it has the capability of anti-cell proliferation by affecting the mevalonic acid pathway.