EFFECT OF ANTIBODY TO TRANSFORMING GROWTH-FACTOR-BETA ON BLEOMYCIN-INDUCED ACCUMULATION OF LUNG COLLAGEN IN MICE
EFFECT OF ANTIBODY TO TRANSFORMING GROWTH-FACTOR-BETA ON BLEOMYCIN-INDUCED ACCUMULATION OF LUNG COLLAGEN IN MICE
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DOI：
10.1136/thx.48.10.959
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发表时间：
1993-10-01
期刊：
影响因子：
10
通讯作者：
HOLLINGER, MA
中科院分区：
文献类型：
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作者：
GIRI, SN;HYDE, DM;HOLLINGER, MA
背景-转化生长因子-β的产生增加似乎在博莱霉素性肺纤维化的病理生理机制中起着重要作用。这归因于转化生长因子-β刺激炎症细胞的渗透和促进结缔组织的合成，导致胶原沉积。方法-本研究旨在评价转化生长因子-β抗体对博莱霉素治疗小鼠肺纤维化的抗纤维化作用。在甲氧氟烷麻醉下，每只小鼠气管内注入50单位无菌等渗盐水或0.125单位博莱霉素50单位。在注射后5分钟内，小鼠尾静脉注射100只非免疫兔抗体、转化生长因子-β2抗体，或不同剂量方案的转化生长因子-β2和转化生长因子-β1抗体的组合。结果：博莱霉素组小鼠肺组织中胶原沉积由445.8(42.3)个/肺减少到336.7(5 6.6)个/肺，博莱霉素组小鼠肺组织胶原沉积明显减少。同样，博莱霉素组大鼠肺组织在注射博莱霉素后，加入250g的转化生长因子-β2抗体和250g的转化生长因子-β1抗体，并于第5天分别注射100杯抗体，也可显著降低博莱霉素诱导的肺组织胶原沉积和髓过氧化物酶活性。结论：转化生长因子-β在博莱霉素性肺纤维化的发病机制中起重要作用，通过全身应用抗体中和转化生长因子-β1，为治疗肺纤维化提供了一种新的药理干预模式。
Background-Increased production of transforming growth factor beta (TGF-beta) seems to have an important role in the pathophysiology of bleomycin induced lung fibrosis. This is attributed to the ability of TGF-beta to stimulate infiltration of inflammatory cells and promote synthesis of connective tissue, leading to collagen deposition.Methods-The study was designed to evaluate the antifibrotic potential of TGF-beta antibody in mice treated with bleomycin, which is a model of lung fibrosis. Under methoxyflurane anaesthesia, each mouse received intratracheally either 50 mul sterile isotonic saline or 0.125 units bleomycin in 50 mul. Within five minutes after the instillation, mice received into the tail vein 100 mul non-immune rabbit IgG, TGF-beta2 antibody, or a combination of TGF-beta2 and TGF-beta1 antibodies at various dose regimens. Mice were killed 14 days after the instillation and their lungs processed for morphological and biochemical studies.Results-Administration of 250 mug of TGF-beta2 antibody after instillation of bleomycin followed by 100 mug on day 5 and 100 mug on day 9 significantly reduced the bleomycin induced increases in the accumulation of lung collagen from 445.8 (42.3) mug/lung to 336.7 (56.6) mug/lung at 14 days. Similarly, the combined treatment with 250 mug TGF-beta2 antibody and 250 mug TGF-beta1 antibody after bleomycin instillation followed by 100 mug of each antibody on day 5 also caused a significant reduction in bleomycin induced increases in lung collagen accumulation and myeloperoxidase activity at 14 days.Conclusions-These results suggest that TGF-beta has an important role in the aetiology of bleomycin induced lung fibrosis; the neutralisation of TGF-beta by systemic treatment with its antibodies offers a new mode of pharmacological intervention which may be useful in treating lung fibrosis.