Histopathological study of the effects of a single intratracheal instillation of surface active agents on lung in rats.
Histopathological study of the effects of a single intratracheal instillation of surface active agents on lung in rats.
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DOI：
10.2131/jts.25.49
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发表时间：
2000-02
期刊：
影响因子：
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通讯作者：
M. Suzuki;M. Machida;K. Adachi;K. Otabe;T. Sugimoto;M. Hayashi;S. Awazu
中科院分区：
文献类型：
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作者：
M. Suzuki;M. Machida;K. Adachi;K. Otabe;T. Sugimoto;M. Hayashi;S. Awazu
大多数多肽/蛋白质类药物肺部给药的特点是通透性低，生物利用度低。表面活性剂已作为吸收促进剂进行了试验，但关于这些添加剂的局部毒性的研究很少。为阐明表面活性物质对大鼠肺的毒性作用，对大鼠一次性气管内滴注较高浓度(1%)的聚氧乙烯-9-十二烷基醚(Laureth-9)和甘氨胆酸钠(SGC)(100微升/只)，观察肺组织病理学变化。在Laureth-9处理的大鼠中，肺损伤发生在从支气管到肺泡的部位。给药后1d可见上皮细胞变性、脱屑所致的水肿、出血和炎性细胞浸润。给药后3d和7d，观察肺损伤所致的创面愈合过程，如上皮细胞增生、散在纤维化等。SGC也可引起类似组织病理学性质的肺部病变，而病变大多局限于肺泡。这些结果表明，表面活性物质通过气管内滴注引起急性肺部炎症，病变在不同表面活性物质中的分布是不同的，此外，在肺给药研究中，病理检查对于阐明吸收促进剂的局部毒性是必不可少的。
Pulmonary drug administration of most peptide/protein drugs is characterized by low bioavailability due to low permeability. Surface active agents have been tested as an absorption enhancer, but few studies have been carried out on the local toxicity of these additives. In the present study, to clarify the toxic effects of surface active agents on the lung, a relatively high concentration (1%) of polyoxyethylene 9 lauryl ether (Laureth-9) and sodium glycocholate (SGC) was given to rats in a single intratracheal instillation (100 microliters/rat), and the lung was evaluated histopathologically. In the rats treated with Laureth-9, lung lesions were observed in the bronchi to alveoli. At 1 day after administration, edema, hemorrhage and inflammatory cell infiltration due to degeneration and desquamation of epithelium were observed. At 3 and 7 days after administration, the wound healing process resulting from the lung injury, such as hyperplasia of epithelium and sporadic fibrosis, was noted. SGC also induced lung lesions with a similar histopathological nature, whereas the lesions were mostly confined to the alveoli. These results suggest that surface active agents induce acute inflammation of the lung by intratracheal instillation, that the distribution of lesions is different among surface active agents, and moreover that pathological examination is indispensable for clarifying local toxicity of absorption enhancers in pulmonary drug-delivery studies.