Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease
Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease
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DOI：
10.1152/ajplung.00210.2013
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发表时间：
2014-04-01
影响因子：
4.9
通讯作者：
Hoffman, Stanley
中科院分区：
文献类型：
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作者：
Lee, Rebecca;Reese, Charles;Hoffman, Stanley
间质性肺疾病包括大量与肺纤维化有关的慢性、进行性、不可逆转的呼吸道疾病，其中最常见的是特发性肺纤维化和硬皮病(SSC ILD)。由于博莱霉素在癌症化疗中使用时会导致肺纤维化，因此它被用来在啮齿动物身上建立人类ILD的模型。在大多数研究中，博莱霉素通过气管内或口腔内给药直接进入肺内。在这里，我们比较了博莱霉素直接进入肺部(直接模型)或系统地使用渗透微泵(泵模型)对小鼠的影响，以确定哪种更接近人类ILD。Pump模型与人SSC ILD的相似之处在于：1)在Pump模型和SSC ILD模型中，肺损伤/纤维化仅限于肺的胸膜下部分，而在DIRECT模型中，整个肺受到影响；2)相反，在DIRECT模型中，肺组织中存在大量炎症，而在Pump模型和SSC ILD中，炎症仅限于肺组织；3)在SSC ILD和SSC ILD模型中，肺泡II型上皮细胞肥大，但在DIRECT模型中不存在；4)肺纤维化伴有真皮纤维化。泵模型也比直接模型移动方便和人性化，因为它的体重减轻和死亡率较低。
The interstitial lung diseases (ILD) include a large number of chronic, progressive, irreversible respiratory disorders involving pulmonary fibrosis, the most common of which are idiopathic pulmonary fibrosis and scleroderma lung disease (SSc ILD). Because bleomycin causes lung fibrosis when used in cancer chemotherapy, it is used to model human ILD in rodents. In most studies, bleomycin has been delivered directly into the lung by intratracheal or intraoral administration. Here we have compared the effects in mice of bleomycin delivered directly into the lungs (direct model) or systemically using osmotic mini-pumps (pump model) to determine which more closely resembles human ILD. The pump model is more similar to human SSc ILD in that: 1) lung injury/fibrosis is limited to the subpleural portion of the lung in the pump model and in SSc ILD, whereas the entire lung is affected in the direct model; 2) conversely, there is massive inflammation throughout the lung in the direct model, whereas inflammation is limited in the pump model and in SSc ILD; 3) hypertrophic type II alveolar epithelial cells are present at high levels in SSc ILD and in the pump model but not in the direct model; and 4) lung fibrosis is accompanied by dermal fibrosis. The pump model is also move convenient and humane than the direct model because there is less weight loss and mortality.