Evaluation of multiorganotrophic factor HGF on the repression of bleomycin induced lung injury and fibrosis in mice

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To examine the involvement of HGF in lung regeneration after injury, the murine lung injured by bleomycin (BLM) with or without administration of human recombinant HGF was studied. Mice 8 to 10 weeks old received BLM (100mg/kg/7days) with continuous s.c.infusion with a minipump (model 2001, Alza Corp.) for lung injury. Low dose HGF (50mug/mouse/7days) and high dose HGF (280mug/mouse/14day) were administrated intraperitoneally. (1)In the examination using low dose HGF,HGF or vehicle was administrated as a i.p.infusion. Two and 4 weeks after treatment, groups of mice were sacrificed. With histologic study, simultaneous administration of low dose HGF with BLM apparently repressed the inflammatory process and showed less fibrotic lesions. Analysis by the numerical fibrotic scale and the point counting method revealed that the grade of fibrotic changes of the lung in the mice using HGF were significantly smaller than those in the mice without HGF at 4 weeks. (2) In the examination with high … More dose HGF,mice were devided into 3 groups. Mice of group I and II received high dose HGF by i.p.infusion from day 1 to 14, and from day 15 to 28, respectively, and group III received vehicle from day 1 to 14. Four weeks after treatment, mice were sacrificed. In comparison with group III (BLM alone), the histologic findings of group I and II revealed that lung damages were apparently repressed. The grades of lung injury of group I,II and III,estimated by the numerical scale, were 2.09 (]SY.+-.]) 0.31,1.97 (]SY.+-.]) 0.24, and 4.91 (]SY.+-.]) 0.14, respectively. The score in group I and II were significantly lower than group III (p<0.001 : ANOVA). These results indicate that administration of HGF in different phases equally repressed BLM induced fibrotic changes in lung. (3) The concentration of HGF in lung, liver kidney at 3 days after initial administration of continuous i.p. of HGF 333 and 50 mug/mouse/7days, were 1.96 (]SY.+-.]) 0.04,47.24 (]SY.+-.]) 14.27,12.10 (]SY.+-.]) 0.71ng/g・tissue, 0.63 (]SY.+-.]) 0.27,5.94 (]SY.+-.]) 2.37,1.62 (]SY.+-.]) 0.18 ng/g・tissue, respectively. Less