實驗室過去研究中指出暴露奈米碳黑微粒會誘導肺部發炎及增加肺泡微血管通透性，先前研究表示血管緊張素II具有調控肺部發炎反應及血管通透性。近年來也有研究表明血管緊張素II與肺損傷具正相關性。但未有研究探討血管緊張素II及其第一型受體於奈米微粒致肺損傷中所扮演的角色。因此此研究主要探討血管緊張素II第一型受體於奈米微粒致肺損傷中所扮演的角色。使用雄性ICR小鼠以口咽吸入方式暴露奈米碳黑微粒(100, 200 μg /mouse)，於暴露後6、16、21及42小時犧牲並採集其肺泡沖提液。於肺泡沖提液中利用trypan blue法計算總發炎細胞數、利用劉氏染色法進行白血球分類計數，也進行肺泡沖提液中總蛋白量分析。酵素免疫分析法測量於肺泡沖提液中血管內皮生長因子和腫瘤壞死因子-α及血液中血管內皮生長因子之表現量。抑制劑實驗則是於小鼠暴露奈米碳黑微粒前30分鐘以腹腔注射血管緊張素II第一型受體抑制劑。結果顯示暴露奈米碳黑微粒21小時後肺泡沖提液中總發炎細胞數、嗜中性白血球數及總蛋白量達到最高且隨著劑量提昇而增加，此結果表示暴露奈米碳黑微粒後發炎反應產生以及肺泡微血管通透性增加。此外肺泡沖提液中血管內皮生長因子表現在暴露後顯著上升並於16小時達到最高，這表明了奈米碳黑微粒暴露之下會使血管內皮生長因子表現量增加且與肺泡微血管通透性增加有關。另外在暴露奈米碳黑微粒前30分鐘腹腔注射血管緊張素II第一型受體抑制劑，可以發現到總發炎細胞數下降、嗜中性白血球聚集減少，也觀察到肺泡沖提液中腫瘤壞死因子-α表現量下降，顯示在奈米碳黑微粒下血管緊張素II第一型受體能夠調控肺部發炎反應。此外，肺泡沖提液中總蛋白量及肺泡沖提液和血液中血管生長因子之表現量也在腹腔注射血管緊張素II第一型受體抑制劑後有下降的趨勢，表示血管緊張素II第一型受體抑制劑能夠降低在奈米碳黑微粒暴露下導致肺泡微血管通透性增加。
綜合以上結果，暴露奈米碳黑微粒確實會導致肺部損傷，且血管緊張素II第一型受體具有調控肺部發炎反應及肺泡微血管通透性。

In this study, we investigated the role of angiotensin II type 1 receptor (AT1R) in ultrafine particle induced lung injury. Male ICR mice were oropharyngeal aspirated with ufCB (0, 100, 200 μg/mouse). For inhibitory study, a group of mice were injected with AT1R antagonist (ZD7155; 20 mg/kg) intraperitoneally 30 min before ufCB aspirated. The total cell counts, differential counts and total protein were measured in bronchoalveolar (BAL) fluid. Enzyme-linked immunosorbent assay (ELISA) was used to measure vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) in BAL fluid, and VEGF in blood. The results show that exposure to ufCB caused a dose-dependent increased the total cell counts, the numbers of neutrophils and total protein in BAL fluid, with the maximal increase at 21 hr. The data indicate that ufCB caused pulmonary inflammatory response and alveolar-capillary permeability. TNF-α was significantly increased at 6 hr. Furthermore, ufCB induced significant productions of VEGF in BAL fluid over the study period, with a maximal increase at 16 hr. Pretreatment with ZD7155 significantly reduced the total cell counts and neutrophils in BAL fluid. ZD7155 also reduced the expression of TNF-α, total protein and VEGF. The results from our study demonstrate that ufCB exposure induced pulmonary inflammatory response and alveolar-capillary permeability may be mediated by AT1R.

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