Exacerbation of Bleomycin-Induced Injury and Fibrosis by Pneumonectomy in the Residual Lung of Mice
Exacerbation of Bleomycin-Induced Injury and Fibrosis by Pneumonectomy in the Residual Lung of Mice
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DOI：
10.1016/j.jss.2008.06.021
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发表时间：
2009-06-15
影响因子：
2.2
通讯作者：
Kobayashi, Koichi
中科院分区：
文献类型：
--
作者：
Kakizaki, Toru;Kohno, Mitsutomo;Kobayashi, Koichi
背景资料。由于局部晚期肺癌分期较低，在诱导化疗和/或放射治疗后行肺切除可合并致死性间质性肺炎。我们研究了肺切除对博莱霉素诱导的小鼠肺损伤和纤维化的影响。在气管内注射生理盐水或博莱霉素后，小鼠接受了左肺切除或假开胸手术。术后7d取剩余右肺测定肺通透性指数、干湿重比、组织学改变、胶原含量、肺泡灌洗液(BAL)中炎性介质浓度和细胞计数。全肺切除后肺毛细血管通透性指数、肺水含量和BAL液炎性细胞计数均显著增加。在肺切除和气管内注射博莱霉素的小鼠中，这些测量结果最高。同样，肺病理中的纤维化改变以及肺胶原含量的增加，在这两种干预措施下的小鼠中最为显著。全肺切除后BAL液中IL-1β、IL-6、RANTES和高迁移率族蛋白1浓度显著升高，而博莱霉素组BAL液中IL-1β、IL-6、RANTES和高迁移率族蛋白1浓度明显升高。这项研究的结果表明，单肺切除可导致非危重肺损伤，从而放大博莱霉素的炎症反应，促进肺纤维化。几种炎症介质似乎参与了博莱霉素性肺损伤和纤维化的加重。(C)2009 Elsevier Inc.保留所有权利。
Background. Lung resection after induction chemotherapy and/or radiotherapy for down-staging of locally advanced lung cancer can be complicated with lethal interstitial pneumonia. We studied the effects of pneumonectomy on bleomycin-induced lung injury and fibrosis in mice.Methods. The mice underwent left pneumonectomy or a sham thoracotomy after intratracheal administration of saline or bleomycin. Lung permeability index, wet-to-dry weight ratio, histological changes, collagen contents, and concentrations of inflammatory mediators and cell counts in broncho-alveolar lavage (BAL) fluid were assessed in the residual right lung 7 d after surgery.Results. The index of capillary permeability, lung water content, and inflammatory cell counts in BAL fluid were significantly increased by pneumonectomy. These measurements were highest in the mice with both pneumonectomy and intratracheal administration of bleomycin. Similarly, fibrotic change in lung pathology, as well as an increase in lung collagen content, was most prominent in the mice exposed to both interventions. The BAL fluid concentrations of interleukin-1 beta, interleukin-6, RANTES, and high mobility group box 1 were significantly increased by pneumonectomy and enhanced by the additional administration of bleomycin.Conclusions. The results of this study indicate that pneumonectomy alone causes noncritical lung injury, which amplifies the inflammatory response to bleomycin and promotes lung fibrosis. Several inflammatory mediators appear to be involved in the exacerbation of bleomycin-induced lung injury and fibrosis. (C) 2009 Elsevier Inc. All rights reserved.