Lossos I S, Izbicki G, Or R, Goldstein R H, Breuer R
Lung Cellular & Molecular Biology Laboratory-Institute of Pulmonology, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Life Sci. 2000 Oct 27;67(23):2873-81. doi: 10.1016/s0024-3205(00)00865-1.
Since transforming growth factor beta (TGF-beta) is presumed to play a role in lung fibrosis, we evaluated the effect of suramin (Sur), a substance with an anti-TGF-beta effect, in vivo on bleomycin (Bleo)-induced pulmonary injury in mice and in vitro on human lung fibroblasts. Four groups of C57BL/6 mice each received one of four treatments: (1) intratracheal (i.t.) instillation of Bleo and intraperitoneal (i.p.) injections of Sur, every other day, starting one day before i.t. instillation of Bleo (Bleo-Sur); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. Sur (Sal-Sur); and (4) i.t. and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage (BAL) fluid, histologically by the semiquantitative morphological index, and biochemically by analysis of lung hydroxyproline content. In vitro, Sur did not affect TGF-beta induced increase of alpha1 (I) collagen mRNA in human lung fibroblasts. In vivo treatment of mice with Sur did not affect Bleo-induced lung injury. These results indicate that despite its potential anti TGF-beta and lymphocytotoxic effects, Sur is not a therapeutic candidate drug for rescue of lung fibrosis.
由于推测转化生长因子β（TGF-β）在肺纤维化中起作用，我们评估了苏拉明（Sur）（一种具有抗TGF-β作用的物质）在体内对博来霉素（Bleo）诱导的小鼠肺损伤以及在体外对人肺成纤维细胞的影响。四组C57BL/6小鼠分别接受以下四种处理之一：（1）在气管内（i.t.）滴注博来霉素前一天开始，每隔一天进行一次气管内滴注博来霉素并腹腔内（i.p.）注射苏拉明（Bleo-Sur）；（2）气管内滴注博来霉素并腹腔内注射生理盐水（Bleo-Sal）；（3）气管内滴注生理盐水并腹腔内注射苏拉明（Sal-Sur）；以及（4）气管内和腹腔内注射生理盐水（Sal-Sal）。在气管内处理后14天处死动物。通过分析支气管肺泡灌洗（BAL）液评估肺损伤，通过半定量形态学指数进行组织学评估，并通过分析肺羟脯氨酸含量进行生化评估。在体外，苏拉明不影响TGF-β诱导的人肺成纤维细胞中α1（I）型胶原mRNA的增加。在体内用苏拉明处理小鼠不影响博来霉素诱导的肺损伤。这些结果表明，尽管苏拉明具有潜在的抗TGF-β和淋巴细胞毒性作用，但它不是用于挽救肺纤维化的候选治疗药物。
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