| 摘要: | 空氣汙染對於人類健康有極大的影響，為造成慢性阻塞性肺病(COPD)其中一大主因。交通空氣汙染為都市空氣汙染的重要來源，但其所產生的懸浮粒子對於罹患慢性阻塞性肺病的可能致病機制仍不清楚。為了解交通汙染懸浮粒子對於肺部蛋白質的影響，我們針對使用大鼠建立的交通空氣汙染三個月和六個月的暴露模型(PM1)其肺臟組織蛋白體進行定量分析，並和吸入使用 high efficiency particulate air-filtered (HEPA)過濾之空氣的組別(GAS)，以及飼養在台北醫學大學動物中心的對照組(CTL)做比較。我們總共鑑定到 2673 個蛋白質，其中暴露三個月的大鼠與其年齡匹配的對照組比較後，PM1 組有 179 個有變化的蛋白質，而 GAS 組有 218 個蛋白質，我們進一步比較 PM1 和 GAS 的差異，發現了 119 個有變化的蛋白質。為了找出與疾病進程相關的因子，我們同時比較 PM1 和 GAS 組三個月到六個月的蛋白質量，其中 PM1 有 413 個有變化的蛋白質而 GAS 組有 408 個有變化的蛋白質。功能性分析的結果發現 PM1 組在三個月就出現調控 oxidative phosphorylation, inositol phosphate synthesis, and acute phase response 的相關蛋白質。顯示分子比起肺功能還要提早出現變化。接著，在疾病進展過程中，PM1 和 GAS 組對於細胞骨架出現不一樣的調控機制，可能暗示著同樣肺功能下降，兩者是不同的表現型。最後，我們還發現當汙染空氣多了懸浮粒子後會對於 RHOA kinase 調控的路徑產生抑制。整體來說，我們觀察到在交通汙染暴露下 PM1 組有相對於 GAS 組更急性的發炎表現。未來將針對交通汙染暴露下肺部損傷時其免疫變化和 COPD 的疾病病程之間的關係。
Exposure to air pollution has been reported to associate with human diseases, especially chronic obstructive pulmonary disease (COPD). The particulate matter (PM)
were reported to induce oxidative stress and cause imbalance of immune system, finally leads to inflammation. However, the role of PM from traffic-related air pollution (TRAP), as one of important air pollution in urban area, in the development of lung
injury remains unclear. In order to investigate the impact of PM on lung injury, we applied lung function characterization and quantitative proteomics analysis on lung tissues from the rat models exposed to TRAP (PM1) with comparison to those exposed to high-efficiency particulate air-filtered air (GAS), and the clean air (CTL) for 3 and 6 months to unveil the progression-related and PM-specific aberrant mechanisms. After
different time point of exposure, the rat models exhibit the decrease of lung function in 6 months, while the histological analysis pointed out an earlier phenotype change I 3 months. The lung tissue proteomics analysis identified a total of 2,673 proteins of which 179 and 218 proteins were differentially expressed in 3-month PM1 and GAS groups in related to CTL group, respectively, while 119 proteins were differentially expressed in
3-month PM1 group compared to GAS group. In addition, 413 and 408 proteins showed progressively differential expressions in PM1 and GAS groups respectively. The
functional analysis indicated the up-regulations of oxidative phosphorylation, inositol phosphate synthesis, and acute phase responses in 3-months PM1 group, suggesting early molecular changes in rat lungs even without significant decreased lung function.
The PM1-exposed rat lungs revealed unbalanced RAC-mediated actin stabilization and suppressed RHOA-mediated migration than GAS-exposed group which implied a
limited repairing ability after lung function decline. Altogether, the rat model exposed to whole TRAP air illustrated PM-specific acute inflammatory regulations and the dysregulation of actin-based tissue repairing system. The more detailed tissue repairing alterations underlying lung injury upon PM1 exposure and its association with COPD development will be the future directions. |
