| 研究生: |
潘奕亘 Pan, Yi-Syuan |
|---|---|
| 論文名稱: |
探討亞慢性呼吸暴露超細微碳黑對大鼠肺部遠端幹細胞之影響 The effects of sub-chronic inhalation exposure to ultrafine carbon black on distal lung stem cells in rats |
| 指導教授: |
張志欽
Chang, Chih-Ching |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 環境醫學研究所 Department of Environmental and Occupational Health |
| 論文出版年: | 2023 |
| 畢業學年度: | 111 |
| 語文別: | 中文 |
| 論文頁數: | 70 |
| 中文關鍵詞: | 細支氣管化 、細支氣管肺泡幹細胞 、Club細胞 、c-Met 、超細微碳黑 |
| 外文關鍵詞: | bronchiolization, bronchoalveolar stem cells, club cell, c-Met, ultrafine carbon black |
| 相關次數: | 點閱:78 下載:0 |
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流行病學指出長期暴露細懸浮微粒(Particulate matter, PM2.5)與肺腺癌的發生增加相關。肺部前驅細胞在修復上皮過程中扮演重要角色,並且在癌症發展同樣至關重要,遠端細支氣管化是肺腺癌發展的早期變化之一,為氣管前驅細胞不正常增生所致。本研究探討亞慢性呼吸暴露超細微碳黑(Ultrafine carbon black, ufCB)對肺部遠端幹細胞的影響。將Wistar公鼠暴露於數目濃度600,000#/cm3的碳黑,進行每天6小時,每週5天,共4週及13週的暴露,於暴露結束後一天犧牲,並以蘇木素-伊紅染色、免疫組織化學染色及免疫螢光染色等組織染色法,觀察肺部終端細支氣管與肺泡管周圍肺泡之細胞組織變化,選取終端細支氣管縱切面,以及其延伸至肺泡管周圍肺泡的視野,進行半定量分析。經H&E染色結果顯示暴露13週後終端細支氣管的上皮細胞異常增生,並在肺泡觀察到可能是肺泡上皮增生或細胞遷移。經4週暴露Club細胞及二型肺泡細胞有增殖的趨勢,而Club細胞、細支氣管肺泡幹細胞與二型肺泡細胞的PCNA增生指數在暴露13週後顯著上升,致癌基因c-Met磷酸化的細胞數目比例在暴露4週後有增加的趨勢,暴露13週後ufCB組在終端細支氣管及肺泡管周圍肺泡中皆顯著上升。
根據研究結果,亞慢性呼吸暴露超細微碳黑會促使肺部遠端幹細胞Club細胞、細支氣管肺泡幹細胞和二型肺泡細胞的增生。
Epidemiological studies have confirmed long-term exposure to fine particulate matter (PM2.5) is associated with the increase of lung adenocarcinoma. Lung progenitor epithelial cells play a critical role in repairing procedure, and play an important role in the development of cancer. Bronchiolization is an important indicator in the early development of lung adenocarcinoma. In this study, we investigate the effects of sub-chronic ultrafine carbon black (ufCB) exposure on distal airway stem cells. Male Wistar rats were exposed by inhalation to 600,000#/cm3 ufCB 6 hours/day, 5 days/week for 4 weeks and 13 weeks. Rats were sacrificed on the day after the last exposure. Hematoxylin and eosin stain, immunohistochemistry stain and immunofluorescence stain were used to examine the change of lung cells. For semi-quantitative analysis, each fields in terminal bronchioles and alveoli were examined. The morphology of lung tissue showed epithelial hyperplasia in terminal bronchiole after ufCB exposure. In alveoli, the epithelial hyperplasia in ufCB group was observed. The PCNA labeling index of club cells, bronchoalveolar stem cells and alveolar type II cells increased significantly after ufCB exposure. After ufCB exposure, the proportion of p-c-Met+ cells was significantly increased in the terminal bronchioles and alveoli around the alveolar ducts. This study suggests that distal lung stem cells proliferated after ufCB exposure.
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校內:2028-08-04公開