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F344大鼠炎症性和致瘤性肺损伤中表面活性蛋白A、B、C和D的免疫组织化学特征

Immunohistochemical characteristics of surfactant proteins a, B, C and d in inflammatory and tumorigenic lung lesions of f344 rats.

作者信息

Yokohira Masanao, Yamakawa Keiko, Nakano Yuko, Numano Takamasa, Furukawa Fumio, Kishi Sosuke, Ninomiya Fumiko, Kanie Shohei, Hitotsumachi Hiroko, Saoo Kousuke, Imaida Katsumi

机构信息

Onco-Pathology, Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.

出版信息

J Toxicol Pathol. 2014 Oct;27(3-4):175-82. doi: 10.1293/tox.2014-0020. Epub 2014 Jun 9.

Abstract

Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically. Formalin fixed paraffin embedded (FFPE) lung samples featuring inflammation were obtained with a rat quartz instillation model, and neoplastic lesions, hyperplasias and adenomas, were obtained with the rat DHPN-induced lung carcinogenesis model. In the rat quartz instillation model, male 10-week old F344 rats were exposed by intratracheal instillation (IT) to quartz at a dose of 2 mg/rat suspended in saline (0.2 ml) on day 0, and sacrificed on day 28. Lung tumorigenesis in F344 male rats was initiated by DHPN in drinking water for 2 weeks, and the animals were then sacrificed in week 30. Lung proliferative lesions, hyperplasias and adenomas, were observed with DHPN, and inflammation was observed with quartz. The expressions of SP-A, SP-B, SP-C and SP-D were examined immunohistochemically. SP-B and SP-C showed strong expression in lung hyperplasias and adenomas, while SP-A and SP-D were observed in mucus or exudates in inflammatory alveoli. These results suggest the possibility that SP-B and SP-C are related to lung tumorigenesis.

摘要

表面活性蛋白(SPs)最初被称为人肺表面活性剂,对呼吸结构和功能至关重要。它有4种亚型,即SP-A、SP-B、SP-C和SP-D,其中SP-A和SP-D具有免疫功能,而SP-B和SP-C具有降低生物界面表面张力的物理化学特性。在本实验中,采用免疫组织化学方法检测并比较了N-双(2-羟丙基)亚硝胺(DHPN)诱导的肺肿瘤病变以及石英注入所致炎症病变中SP-A、SP-B、SP-C和SP-D的表达。利用大鼠石英注入模型获取了具有炎症的福尔马林固定石蜡包埋(FFPE)肺样本,并利用大鼠DHPN诱导的肺癌发生模型获取了肿瘤病变、增生和腺瘤样本。在大鼠石英注入模型中,于第0天经气管内注入(IT)将剂量为2mg/只的石英悬浮于生理盐水(0.2ml)中,对10周龄雄性F344大鼠进行暴露,并于第28天处死。通过在饮用水中加入DHPN启动F344雄性大鼠的肺肿瘤发生,持续2周,然后在第30周处死动物。观察到DHPN导致肺增殖性病变、增生和腺瘤,石英导致炎症。采用免疫组织化学方法检测SP-A、SP-B、SP-C和SP-D的表达。SP-B和SP-C在肺增生和腺瘤中呈强表达,而SP-A和SP-D在炎性肺泡的黏液或渗出物中可见。这些结果提示SP-B和SP-C可能与肺肿瘤发生有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0525/4217230/b008a3a5f3a7/tox-27-175-g001.jpg

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