當我們進入21世紀，一種新的粒子種類-極端細微的粒子(ultrafine particle)-已經顯露出它對於疾病的影響及扮演一個很有潛力的角色。一般說來，ultrafine particle是指粒徑小於100nm的細微粒子。最近在毒物學的研究中預測在同等的質量濃度下，有一些ultrafine particle毒性比fine particle來的更強；而ultrafine particle 可以直接穿過肺的組織並造成在肺泡堆積。在我們的研究裡，發現ultrafine carbon particle (ufCB)能在A549細胞中刺激活性氧分子(ROS)的生成。在小鼠的動物模型中，由ufCB刺激產生的活性氧分子(ROS)會引起上皮細胞傷害(Epithelial damage)，而藉由觀察血管內皮的鈣離子依賴性黏著分子(Vascular endothelial cadherin, VE-cadherin)的蛋白下降表現去推測肺泡血管間的通透性(alveolar-capillary permeability)增加；並且藉由觀察在肺中的肺水堆積去判定急性肺發炎(acute lung injury)。

　　近年來，有些研究團隊認為用肺泡沖洗液(BAL fluid)來研究肺部蛋白質體學(Lung proteome)是可行的。而肺泡沖洗液(BAL fluid)也已經被使用在肺部疾病的診斷及肺部發言的研究。依遽Markus Schirle et al (2003)的報告指出，一個簡單的方法-一維膠電泳(One-dimensional gel electrophoresis, 1-DE)結合液相層析-串聯式質譜儀 (Liquid Chromatography Tandem mass spectrometry, LC-MS/MS) (GeLC-MS/MS)，已經變成了一種在蛋白質體學分析中很有用的工具。而在我們的研究中，我們也利用了這個分析方法(GeLC-MS/MS)來分析研究肺泡沖洗液(BAL fluid)。超過65個蛋白從50μg的肺泡沖洗液(BAL fluid)蛋白被鑑定出，而這些蛋白中包含了很多血漿蛋白(plasma proteins)、蛋白脢抑制劑(protease inhibitor)和抗氧化物(antioxidant)。

　　一般來說，在肺泡沖洗夜(BAL fluid)觀察血漿蛋白(plasma)的濃度是一種判定發炎很重要的特徵；而血管內皮生長因子(Vascular endothelial growth factor, VEGF)在肺泡沖洗液(BAL fluid)中的蛋白量則是一個很重要的通透性指標。在我們的研究中，在肺泡沖洗液(BAL fluid)血清白蛋白(albumin)的濃度會隨著用ufCB刺激而增加，並且與血管內皮生長因子(VEGF)的產生量有高度的正相關。而與血清白蛋白(albumin)的功能做比較，α2-巨球蛋白(α2-Macroglobulin)有相似的影響並且推測其為更好的氣管中血漿蛋白(plasma)釋出的指標，而且推測它有很好的潛力去作為一個判斷血管通透性(Capillary permeability)的生物指標(Biomarker)。

　　As we enter the 21st century, a new particle type—the ultrafine particle—has emerged as one with a potential role in causing disease. Particles that are less than 100 nm in diameter are commonly defined as ultrafine. Recent toxicological studies indicate that some ultrafine particles are more toxic than fine particles at an equal mass concentration and ultrafine particles can penetrate directly in the lung tissues and deposited in the alveoli. In our study, ufCB can stimulate the production of ROS in A549 cells. The ufCB-induced ROS production would cause the epithelial damage to increase alveolar-capillary permeability with a decrease in the expression of VE-cadherin and fluid accumulation in alveolar to induce the acute lung injury in murine model.

　　Recently, some research groups demonstrated that approaching the lung proteome is possible using BAL fluid. Evaluation of BAL fluid has been useful in diagnosis and research of several inflammatory lung diseases. According to the report of Markus Schirle et al (2003), a simple method, one-dimensional gel electrophoresis (1-DE) combined with nano-Liquid Chromatography Tandem mass spectrometry (nano-LC/MS/MS) (GeLC-MS/MS), has been applied as a power approaches for the proteome analysis of bronchoalveolar lavage (BAL) in our study. Up to 65 proteins were identified from 50 μg of total proteins including common components of plasma, protease inhibitor or antioxidant.

　　Generally speaking, plasma leakage in BAL is an important feature of inflammation and the protein abundance of VEGF is an important permeability factor. In our study, albumin concentration in BAL increases in ufCB exposure and is highly related to VEGF production. Compared with the function of albumin, α2-Macroglobulin is similar to albumin and has been suggested to better reflect the plasma leakage in the airways and more potential to be a biomarker in capillary permeability.

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