Wang Q, Wang Y, Hyde D M, Gotwals P J, Koteliansky V E, Ryan S T, Giri S N
Department of Molecular Biosciences, University of California, Davis, California 95616, USA Biogen Inc, Cambridge, Massachusetts 02142, USA.
Thorax. 1999 Sep;54(9):805-12. doi: 10.1136/thx.54.9.805.
Transforming growth factor beta (TGF-beta) is a key mediator of collagen synthesis in the development of lung fibrosis. It has previously been shown that the administration of TGF-beta antibody and TGF-beta binding proteoglycan, decorin, reduced bleomycin (BL) induced lung fibrosis in animals. The present study was carried out to investigate whether intratracheal instillation of TGF-beta soluble receptor (TR) would minimise the BL induced lung fibrosis in hamsters.
The effect of a recombinant TR (TGFbetaRII) on the lung collagen accumulation was evaluated in a BL hamster model of pulmonary fibrosis. Animals were divided into four groups and intratracheally injected with saline or BL at 6.5 U/4 ml/kg followed by intratracheal instillation of phosphate buffered saline (PBS) or 4 nmol TR in 0.3 ml twice a week. Twenty days after the first intratracheal instillation the hamsters were killed for bronchoalveolar lavage (BAL) fluid, biochemical, and histopathological analyses.
Treatment of hamsters with TR after intratracheal instillation of BL significantly reduced BL induced lung fibrosis as shown by decreases in the lung hydroxyproline level and prolyl hydroxylase activity, although they were still significantly higher than those of the saline control. Histopathological examination showed a considerable decrease in BL induced fibrotic lesions by TR treatment. However, TR did not prevent the BL induced increases in total cells and protein in the BAL fluid.
These results suggest that TR has antifibrotic potential in vivo and may be useful in the treatment of fibrotic diseases where increased TGF-beta is associated with excess collagen accumulation.
转化生长因子β（TGF-β）是肺纤维化发展过程中胶原蛋白合成的关键介质。先前的研究表明，给予TGF-β抗体和TGF-β结合蛋白聚糖（核心蛋白聚糖）可减轻博来霉素（BL）诱导的动物肺纤维化。本研究旨在探讨气管内滴注TGF-β可溶性受体（TR）是否能使BL诱导的仓鼠肺纤维化降至最低。
在BL诱导的仓鼠肺纤维化模型中评估重组TR（TGFβRII）对肺胶原积累的影响。将动物分为四组，气管内注射生理盐水或6.5 U/4 ml/kg的BL，随后每周两次气管内滴注0.3 ml磷酸盐缓冲盐水（PBS）或4 nmol TR。首次气管内滴注20天后，处死仓鼠以进行支气管肺泡灌洗（BAL）液、生化和组织病理学分析。
气管内滴注BL后用TR治疗仓鼠，可显著减轻BL诱导的肺纤维化，表现为肺羟脯氨酸水平和脯氨酰羟化酶活性降低，尽管仍显著高于生理盐水对照组。组织病理学检查显示，TR治疗可使BL诱导的纤维化病变明显减少。然而，TR并不能阻止BL诱导的BAL液中总细胞数和蛋白含量增加。
这些结果表明，TR在体内具有抗纤维化潜力，可能有助于治疗TGF-β升高与胶原蛋白过度积累相关的纤维化疾病。
