[Losartan in the rat model of bleomycin-induced pulmonary fibrosis and its impact on the expression of monocyte chemoattractant protein-1 and basic fibroblast growth factor].
OBJECTIVE
To study the effect of losartan on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism.


METHODS
Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin. Then the rats received daily losartan 10 mg/kg (group L), prednisone 20 mg/kg (group P), or normal saline (group B) orally. Normal controls received normal saline both intratracheally and orally. Six rats in each group were sacrificed 3, 7, 14, 28 and 56 days after intratracheal instillation. Histological changes of the lungs were evaluated by HE stain, Masson's trichrome stain and sirius red stain. Collagen content of the lung tissue was assessed by hydroxyproline concentration. The mRNAs of monocyte chemoattractant protein-1 (MCP-1) and basic fibroblast growth factor (bFGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Lung expression of MCP-1 and bFGF proteins was assessed by immunohistochemistry and the level of MCP-1 protein was further measured by ELISA.


RESULTS
Pulmonary fibrosis of group L and group P was improved as compared with that of group B. Hydroxyproline concentrations of group L and group P were lower than that of group B. Protein expression of MCP-1 and bFGF in group L was lower than that in group B.


CONCLUSIONS
Losartan alleviates bleomycin-induced pulmonary fibrosis in rats. Inhibiting the expressions of MCP-1 and bFGF in lung tissues may be one of the mechanisms.
Department of Respiratory Disease, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China.
Xiangqun
X
Fang
Yuanjue
Y
Zhu
Xiaoling
X
Hu
Yongjian
Y
Liu
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D018932:Chemokine CCL2; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D001761:Bleomycin; D003094:Collagen; D019808:Losartan; D011241:Prednisone