[Effect of imatinib mesylate on bleomycin-induced pulmonary fibrosis in mice].
OBJECTIVE
To observe the effect of tyrosine kinase depressor imatinib mesylate on pulmonary fibrosis (PF) induced by bleomycin in mice and explore its mechanism.


METHODS
One hundred and twenty C57BL/6 mice were randomly divided into control group, model group, dexamethasone group and imatinib mesylate group (with 30 mice each). After the model of PF was reproduced by a single intratracheal instillation of bleomycin, the above-mentioned drugs were given respectively. On 7, 14 and 21 days after treatment, 10 mice of each group were sacrificed, their lungs were harvested for measurement of the lung index, pathological change, concentration of hydroxyproline (HYP) and expression of platelet-derived growth factor-BB (PDGF-BB) in lung tissues.


RESULTS
Lung indexes of model group were significantly higher than those of control group at different time points after in tracheal bleomycin (all P<0.05). Alveolitis grades and PF degrees were elevated markedly (all P<0.01). The concentrations of HYP in lung tissues were continuously increasing with the elapse of time after bleomycin (all P<0.05). The contents of PDGF-BB were obviously higher than those of control group (all P<0.05), and they gradually reduced with time. In imatinib mesylate and dexamethasone groups alveolitis grades and PF induced by bleomycin were obviously alleviated. The concentration of HYP and expression of PDGF-BB in lung tissues decreased in imatinib mesylate and dexamethasone groups compared with those in model group (P<0.05 or P<0.01). The effects of imatinib mesylate on above indexes were better than those of dexamethasone but without significant differences (all P>0.05).


CONCLUSIONS
Imatinib mesylate may obviously inhibit the development of PF induced by bleomycin in mice.
Li
Li
L
Department of Respiratory Medicine, Renji Hospital, Medical College of Shanghai Jiaotong University, Shanghai, China.
Li
Yan-Qin
YQ
D000818:Animals; D000077214:Becaplermin; D001549:Benzamides; D001761:Bleomycin / Q000633:toxicity*; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000378:metabolism; D000068877:Imatinib Mesylate; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020574:Proto-Oncogene Proteins c-sis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000627:therapeutic use*; D011897:Random Allocation
D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D001761:Bleomycin; D000077214:Becaplermin; D000068877:Imatinib Mesylate; D006909:Hydroxyproline