Effect of pravastatin on bleomycin-induced acute lung injury and pulmonary fibrosis.
1. Pravastatin is best known for its antilipidemic action. Recent studies have shown that statins have immunomodulatory and anti-inflammatory effects. The present study aimed to determine whether or not pravastatin can attenuate acute lung injury and fibrosis in a mouse model. 2. Bleomycin was given to C57BL6 mice through intratracheal instillation. Pravastatin was given through intraperitoneal injection. To study the effect of pravastatin on the early inflammatory phase and the late fibrotic phase, mice were killed on days 3, 7, 14 and 21. 3. Pravastatin attenuated the histopathological change of bleomycin-induced lung injury and fibrosis. The accumulation of neutrophils and increased production of tumor necrosis factor-α in bronchoalveolar lavage fluid were inhibited in the early inflammatory phase. Pravastatin effectively inhibited the increase of lung hydroxyproline content induced by bleomycin. Furthermore, pravastatin reduced the increased expression of transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), RhoA and cyclin D1. The increased levels of TGF-β1 and CTGF mRNA expression were also significantly inhibited by pravastatin. 4. Pravastatin effectively attenuated bleomycin-induced lung injury and pulmonary fibrosis in mice. Our results provide evidence for the therapeutic potential of pravastatin in the treatment of acute lung injury and pulmonary fibrosis.
Kim
Jin Woo
JW
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Catholic University of Korea, Seoul, Korea.
Rhee
Chin Kook
CK
Kim
Tae Jung
TJ
Kim
Yong Hyun
YH
Lee
Sang Haak
SH
Yoon
Hyung Kyu
HK
Kim
Seok Chan
SC
Lee
Sook Young
SY
Kwon
Soon Suk
SS
Kim
Kwan Hyung
KH
Kim
Young Kyoon
YK
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000633:toxicity*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012128:Respiratory Distress Syndrome / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D020742:rhoA GTP-Binding Protein
D000893:Anti-Inflammatory Agents; C526318:CCN2 protein, mouse; C530105:Ccnd1 protein, mouse; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D019938:Cyclin D1; D055513:Connective Tissue Growth Factor; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D017035:Pravastatin; D006909:Hydroxyproline