Objective To observe the effects of different doses of atorvastatin on bleomycin-induced pulmonary fibrosis in rats. Methods Seventy-five healthy female SD rats were randomly divided into five groups ( 15 rats in each group) , ie. a normal group , a model group, a 10 mg/ kg atorvastatin-treated group, a 20 mg/ kg atorvastatin-treated group, and a 40 mg/ kg atorvastatin-treated group. The rats in the model group and treatment groups were instilled with bleomycin in trachea( 5 mg/kg) , and the normal group were instilled with equal volume of normal saline. The treatment groups were gastric gavaged with different doses of atorvastatin each day from2 nd day on after instillation, and the normal group and model group were gavaged with normal saline. Blood samples were obtained from abdominal aorta in five rats in each group and blood gas analysis was performed on1st week, 2nd week and 4th week respectively after BLM instillation. Then the animals were killed and lung tissue samples were harvested for histopathology study. HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis respectively.
Histoimmunochemical stain were used to determine the protein levels of transforming growth factor-β1 ( TGF-β1 ) and connective tissue growth factor( CTGF) in pulmonary tissues. Results The arterial partial pressure of oxygenate ( PaO2 ) in the treatment groups were increased gradually with the increasing of therapeutic dose at each time point and decreased with prolongation of time in the same group. The protein levels of TGF-β1 and CTGF in pulmonary tissues were decreased gradually with prolongation of time. TGF-β1 and CTGF expressed obviously less in the treatment groups than those in the model group at each time point .The higher therapeutic doses were, the less the expressions of TGF-β1 and CTGF were. Conclusion Atorvastatin has remarkable inhibitory effects on BLM-induced pulmonary fibrosis of rats in a dose- and timedependent
manner.
Citation：
ZHANG Xiaoping,SHAO Runxia,LI Fuhua. Effects of Different Doses of Atorvastatin on Pulmonary Fibrosis of Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(6): 580-584. doi:
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Copyright © the editorial department of Chinese Journal of Respiratory and Critical Care Medicine of West China Medical Publisher. All rights reserved
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王浩凌, 谢敏, 刘涛. γ干扰素对博莱霉素诱导的大鼠肺纤维化的干预作用. 中国呼吸与危重监护杂志, 2007, 6: 105-109.
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- 1. Nègre-Aminou P, van Vliet AK, van Erck M, et al. Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibitors; comparison with other human cell types. Biochim Biophys Acta, 1997, 1345: 259-268.
- 2. Snider GL, Celli BR, Goldstein RH, et al. Chronic interstitial pulmonary fibrosis produced in hamasters by endotracheal bleomycin.Am Rev Respir Dis, 1978, 117: 289-297.
- 3. Wen FQ, Kohyama T, Sk ld CM, et al. Glucocorticoids molecular TGF-beta production by human fetal lung fibroblast. Inflammation,2003, 27: 9-19.
- 4. Crean JK, Finlay D,Murphy M, et al. The role of p42 / p44 MAPKand protein kinase B in connective tissue growth factor induced extracellular matrix protein production, cell migration, and actin cytoskeletal rearrangement in human mesangial Cells. J Biol Chem,2002, 277: 44187-44194.
- 5. 王浩凌, 谢敏, 刘涛. γ干扰素对博莱霉素诱导的大鼠肺纤维化的干预作用. 中国呼吸与危重监护杂志, 2007, 6: 105-109.
- 6. Bellosta S, Ferri N, Arnaboldi L, et al. Pleiotropic effects of statins in athero sclerosis and diabetes. Diabetes Care, 2000, 23 : B72 -B78 .
- 7. Watts KL, Sampson EM, Schultz GS, et al. Simvastatin Inhibits Growth Factor Expression and modulates profibrogenic markers in lung fibroblasts. AmJ Respir Cell Mol Biol, 2005, 32: 290- 300.
