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聚六亚甲基胍诱导的大鼠肺损伤的 CT、病理和 RNA 测序评价。

Evaluation of polyhexamethylene guanidine-induced lung injuries by chest CT, pathologic examination, and RNA sequencing in a rat model.

机构信息

Department of Radiology, Ansan Hospital, Korea University College of Medicine, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi, 15355, South Korea.

Research Institute for Skin Image, Korea University College of Medicine, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi, 15355, South Korea.

出版信息

Sci Rep. 2021 Mar 18;11(1):6318. doi: 10.1038/s41598-021-85662-z.

DOI:10.1038/s41598-021-85662-z
PMID:33737587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7973781/
Abstract

Our aim was to correlate chest CT and pathologic findings of polyhexamethylene guanidine phosphate (PHMG)-induced lung injuries in a rat model, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT. A PHMG solution was intratracheally administrated to 40 male rats. Chest CT was carried out in all rats and both lungs were collected for histopathologic evaluation. At 4- and 8-weeks post-instillation, one lobe of the right lung from 3 rats was subjected to RNA sequencing. At least one abnormal CT finding was found in all rats at all weeks. The major CT findings were inflammation, fibrosis, and tumors in the pathologic analysis, where significant changes were observed over time. The lung lesions remained persistent after 8 weeks of PHMG exposure. In the pathologic analysis, the extent/severity of inflammation did not show statistically significant changes over time, whereas the extent/severity of fibrosis increased continuously up to 6 weeks after PHMG exposure and then decreased significantly at 8 weeks. Bronchiolar-alveolar adenomas which have malignant potential were found in 50% of rats at 6 and 8 weeks after PHMG exposure. Also, several genes associated with lung cancer, acute lung injury, and pulmonary fibrosis were detected. Our study revealed that PHMG-induced lung injury and its changes according to the number of weeks after exposure were demonstrated using chest CT and pathologic evaluation. In addition, we showed that PHMG exposure caused lung tumors and genetic alterations according to PHMG exposure under the guidance of CT.

摘要

我们的目的是将聚六亚甲基胍磷酸盐(PHMG)诱导的大鼠肺损伤的胸部 CT 和病理发现相关联,以确定 PHMG 暴露是否会导致肺肿瘤,并根据 CT 引导下的 PHMG 暴露探索遗传改变。将 PHMG 溶液经气管内滴注至 40 只雄性大鼠。所有大鼠均进行胸部 CT 检查,并收集双侧肺进行组织病理学评估。在滴注后 4 周和 8 周时,从 3 只大鼠的右肺一叶进行 RNA 测序。所有大鼠在所有时间点均发现至少一项异常 CT 发现。主要 CT 发现是炎症、纤维化和肿瘤,在病理分析中观察到随时间的显著变化。PHMG 暴露 8 周后肺部病变仍持续存在。在病理分析中,炎症的程度/严重程度随时间无统计学意义的变化,而纤维化的程度/严重程度在 PHMG 暴露后持续增加至 6 周,然后在 8 周时显著下降。在 PHMG 暴露后 6 周和 8 周时,发现 50%的大鼠存在具有恶性潜能的细支气管肺泡腺瘤。此外,还检测到与肺癌、急性肺损伤和肺纤维化相关的几个基因。我们的研究表明,使用胸部 CT 和病理评估可以显示 PHMG 诱导的肺损伤及其在暴露后数周的变化。此外,我们还表明,在 CT 引导下的 PHMG 暴露会导致肺肿瘤和遗传改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/a8c4d1ee074b/41598_2021_85662_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/4b165123ca98/41598_2021_85662_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/db0646be7e06/41598_2021_85662_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/d4aedee6b048/41598_2021_85662_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/499a47e22aa4/41598_2021_85662_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/e6c9f2cd9ee2/41598_2021_85662_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/a8c4d1ee074b/41598_2021_85662_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/4b165123ca98/41598_2021_85662_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/db0646be7e06/41598_2021_85662_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/d4aedee6b048/41598_2021_85662_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/499a47e22aa4/41598_2021_85662_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/e6c9f2cd9ee2/41598_2021_85662_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf3c/7973781/a8c4d1ee074b/41598_2021_85662_Fig6_HTML.jpg

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