流行病學已指出，長期暴露於細懸浮微粒(Particulate matter, PM2.5)會使得肺腺癌發生率增加31%，國際癌症研究署(IARC)已將室外PM2.5歸類為人類一級致癌物。二型肺泡細胞被認為是肺腺癌的起始細胞之一，但目前模擬長期暴露於空氣中超細懸浮微粒對二型肺泡細胞之增生情形尚不明瞭。因此本研究探討亞慢性奈米碳黑呼吸暴露後肺上皮細胞受損、增生情形，以及致癌基因c-Met的活化。本研究以電腦程式控制呼吸暴露艙進行亞慢性奈米碳黑(Ultrafine carbon black, ufCB)暴露，將Wistar公鼠以600,000#/cm3的數目濃度，進行每天6小時，每週暴露5天，為期13週的暴露，並在暴露結束後一天犧牲。實驗結果顯示亞慢性奈米碳黑呼吸暴露後，肺沖提液中總發炎細胞計數在暴露後相較過濾空氣控制組或管錐控制組並未顯著上升，且白血球分類計數以巨噬細胞表現為主，並未觀察到嗜中性白血球的浸潤。而乳酸脫氫酶指標與過濾空氣控制組或管錐控制組相比在暴露13週後上升；鎖鏈素則在暴露後未顯著上升。H&E染色中在暴露組可見上皮細胞的增生或肉芽腫性的發炎，而在IHC染色結果中，二型肺泡細胞增生指數在暴露後顯著上升；肺上皮細胞染上p-c-Met的比例在暴露組中與過濾空氣控制組或管錐控制組相比皆顯著上升。
綜合以上結果，亞慢性呼吸暴露奈米碳黑後，總細胞計數、鎖鏈素雖未顯著增加，但在肺泡仍觀察到肺上皮細胞的增生，肺上皮細胞染上p-c-Met的比例也顯著上升。未來仍需進一步探討c-Met活化於呼吸暴露奈米碳黑後在早期病理變化中所扮演的腳色。

Epidemiological studies have shown that long-term exposure to fine particulate matters(PM2.5) is associated with the development of lung adenocarcinoma. International Agency for Research on Cancer(IARC) has classified outdoor particulate matters as a Group 1 carcinogen to humans. In this study, we investigated the pulmonary epithelial cells injury and proliferation following sub-chronic exposure to ultrafine carbon black inhalation. Wistar rats were exposed nose-only to ufCB(600,000 #/cm3, 6 hour/day, 5 day/week) for 13 weeks. One day after the last exposure, rats were sacrificed. Result showed that there were no significantly increased in total inflammatory cells, including neutrophils, after 13 weeks exposure. However, lactate dehydrogenase(LDH) activity was significantly increased in ufCB exposure group, which suggested that lung epithelial cells were injured after sub-chronic inhalation exposure. Nevertheless, basement membrane might be still intact, due to non-significant change of desmosine in the bronchoalveolar lavage fluid(BALF). Histopathological examination of lung tissue showed that epithelial cells hyperplasia and granulomatous inflammation occurred in alveolar region in ufCB group. The increased percentage of type II cells stained positively for PCNA(PCNA labeling index), c-Met and p-c-Met staining was observed in ufCB group by IHC staining. This study suggests that the activation of c-Met may play a role in the proliferation of alveolar type II cells. Further study is warranted to explore the role of c-Met activation in ultrafine carbon black-induced early pathological changes.

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