原發性肺纖維化是一種慢性間質性肺病，肺纖維化漸進持續形成，以致預後不良。我們先前的研究發現暴露奈米碳管和二氧化矽皆會誘發肺纖維化，且肺二型上皮細胞可轉化並貢獻超過四成的新生肺纖維細胞。本研究主要釐清肺泡二型上皮細胞、血管內皮前驅細胞和循環纖維細胞如何參與奈米碳管和二氧化矽誘發肺纖維化的形成及其空間浸潤分佈關係。
使用C57BL6母鼠以口咽吸入方式暴露奈米碳管80 μg/mouse或二氧化矽512 μg/mouse，分別至不同時間點(2週、4週、6週)後犧牲。利用流式細胞儀分析技術和免疫螢光染色肺連續切片，觀察組織血管內皮前驅細胞、循環纖維細胞和肺泡二型的浸潤及轉化，其對肺纖維化的貢獻和彼此空間分佈相關性。
結果顯示暴露奈米碳管後，發現第6週之血管內皮前驅細胞和循環纖維細胞分別有27.30% 和25.75%參與纖維化中纖維細胞數目的擴張，導致纖維化的發生。在暴露奈米碳管的組別，觀察到血管內皮前驅細及循環纖維細胞同時轉移至受損區域轉化成纖維細胞及纖維母細胞，且彼此交錯，肺泡二型上皮細胞及其轉化的纖維細胞也參雜在其中，形成了增生纖維細胞病灶，但這種明顯的病灶變化在暴露二氧化矽的組別並沒有發生。此外，在暴露奈米碳管後CD133+細胞數目與纖維轉化相關蛋白活化因子p-Smad2、Ras和Snail表現量會隨著暴露時間而增加。總結，奈米碳管暴露，造成血管內皮前驅細胞和循環纖維細胞的肺部浸潤並轉化成纖維細胞和纖維母細胞，這些細胞和肺泡二型上皮細胞及其轉化的的纖維細胞一起形成增生纖維細胞病灶，這可能是人類特發性肺纖維化重要特徵之一的纖維母細胞病灶的前驅。但二氧化矽暴露並不造成增生纖維細胞病灶的形成。

The goal of our research is aimed to describe the involvement of alveolar type II cells, EPCs and fibrocytes during CNT and silica-induced pulmonary fibrosis and their spatial relationship.Female C57BL/6 mice were oropharyngeally aspirated with 80 μg SWCNT or silica 512 μg.Flow cytometry analysis indicated that EPCs and fibrocytes were involved in the expansion of fibroblasts, contributing to 27.30% and 25.75% of total fibroblasts, respectively, at 6 wks post exposure to CNT. Importantly, EPCs and fibrocytes were found to be interspersed with each other, and with type II cells and their derived fibroblast in the same foci in the CNT group. However, these did not happen in the silica exposure group. In summary, EPCs and fibrocytes infiltrate the injury lung and are turned into fibroblasts/myofibroblasts, together with type II cells-transitioned fibroblasts, to form fibroproliferative foci, which may later become myofibroblastic foci. There is no obvious fibroproliferative foci found in silica-exposed mice.

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