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

多器官营养因子HGF抑制博来霉素诱导的小鼠肺损伤和纤维化的评价

基本信息

批准号：
06454270
负责人：
NUKIWA Toshihiro
金额：
$ 4.54万
依托单位：
Institute of Development, Aging and Cancer, Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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

为了检测HGF在损伤后肺再生中的参与，研究了在施用或不施用人重组HGF的情况下由博莱霉素（BLM）损伤的小鼠肺。8至10周龄的小鼠接受BLM（100 mg/kg/7天），用微型泵（型号2001，Alza Corp.）治疗肺部损伤腹腔注射低剂量HGF（50 μ g/小鼠/7天）和高剂量HGF（280 μ g/小鼠/14天）。(1)In使用低剂量HGF、HGF或赋形剂的检查以腹膜内输注的方式施用。治疗后2周和4周，处死各组小鼠。组织学研究表明，低剂量HGF与BLM同时给药明显抑制了炎症过程，并显示出较少的纤维化病变。通过数值纤维化量表和点计数法的分析显示，在4周时，使用HGF的小鼠的肺纤维化变化的等级显著小于未使用HGF的小鼠。(2)在考试中， ...更多信息 HGF剂量组，将小鼠分为3组。组I和组II的小鼠分别从第1天至第14天和从第15天至第28天通过腹膜内输注接受高剂量HGF，组III从第1天至第14天接受媒介物。处理后四周，处死小鼠。与组III（BLM单独）相比，组I和组II的组织学结果显示，肺损伤明显受到抑制。I、II、III组的肺损伤程度按数值评分法分别为2.09（[SY. ±.]）0.31，1.97（]SY.+-.]）0.24和4.91（[SY. ±.]）0.14，分别。组I和组II的评分显著低于组III（p<0.001：ANOVA）。这些结果表明，在不同阶段给予HGF同样抑制BLM诱导的肺纤维化变化。(3)连续腹腔注射HGF 333和50 μ g/小鼠/7天后第3天，肺、肝、肾中HGF浓度分别为1.96（± SD）和1.96（± SD）。0.04，47.24（]SY.+-.]）14.27，12.10（]SY.+-.]）0.71ng/g·组织，0.63（[SY. ±.]）0.27，5.94（]SY.+-.]）2.37，1.62（]SY.+-.]）0.18 ng/g·组织。少