目前流行病學證據指出不論是短期或長期暴露於細懸浮微粒下，皆會增加罹患肺部和心血管疾病伴隨血壓增加的風險；動物實驗也證實暴露細懸浮微粒會造成肺部損傷和血管內皮功能失調。此外，空氣中所含的細懸浮微粒粒子數最多的是超細微粒或奈米微粒，先前本實驗室證明奈米碳黑 (14 nm)誘發血管內皮生長因子，造成肺泡-微血管通透性增加及肺水腫。血管收縮素II參與內皮功能失調、高血壓等病態生理的發展及調控血管內皮生長因子的表現，目前對於血管收縮素II及其第一型受體於奈米微粒誘發肺部損傷中所扮演的角色還尚未明瞭。
為探討血管收縮素II及其第一型受體於奈米微粒誘發肺部損傷所扮演的角色，利用SD公鼠以口咽吸入法，重複暴露4 mg/kg的奈米碳黑、奈米銀及奈米二氧化鈦(每96小時暴露一次，共三次)，於最後一次暴露96小時後犧牲，採其血液、肺沖提液以酵素連結免疫法分析發炎及內皮損傷指標，接著利用肺均質液進行流式細胞儀分析肺泡二型上皮細胞，最後收其組織進行包埋及切片染色。
結果顯示暴露奈米碳黑、奈米銀和奈米二氧化鈦造成肺沖提液中總蛋白量和血管內皮生長因子顯著增加，組織切片染色和流式細胞儀分析結果顯示肺水腫和肺泡二型上皮細胞不正常的增加，這結果顯示暴露奈米微粒會造成肺部損傷。血漿血管收縮素II及血清血管內皮生長因子、細胞間黏附分子、E-選擇素的表現量增加，為進一步驗證血管收縮素II經由其第一型受體於奈米微粒引起肺部損傷之貢獻，於暴露前30分鐘腹腔注射血管收縮素II第一型受體拮抗劑Losartan能夠有效降低肺部損傷和血清血管內皮生長因子和細胞間黏附分子的表現量，此外血清血管內皮生長因子和細胞間黏附分子的增加分別和肺泡二型上皮細胞的增加具有顯著相關性，以上結果可知血管收縮素II及其第一型受體參與調控奈米微粒誘發肺損傷，Losartan拮抗劑能使奈米微粒誘發肺損傷和血管內皮生長因子及細胞間黏附分子之表現量顯著下降，此外，血清血管內皮生長因子和細胞間黏附分子可能為奈米微粒誘發肺部損傷之生物指標。未來將持續研究血管收縮素II及其第一型受體訊息於奈米微粒誘發肺損傷和內皮功能失調所扮演的角色。

We aimed to investigate the role of Angiotensin II (AngII) and its receptor signaling in nanoparticles-induced pulmonary injury and their potential as biomarkers for early injury detection. SD rats were oropharyngeally aspirated (3 times, at 96 hr interval) with 4 mg/kg ultrafine carbon black (ufCB), nano Ag (AgNPs) and nano TiO2. The results indicate that exposure to ufCB, AgNPs and TiO2 caused significant increases of total proteins and VEGF. Histological examination and flow cytometry demonstrated significant pulmonary edema and proliferation of SPC+ alveolar type II cells, respectively. These are indicators of pulmonary injury. Plasma AngII, serum VEGF, ICAM-1 and E-selectin were also significantly elevated. Pretreatment with Ang II type I receptor (AT1R) antagonist losartan caused significant reductions in pulmonary injury, and serum VEGF and ICAM-1. Importantly, there were significant correlations between serum VEGF or ICAM-1 and pulmonary percent SPC+PCNA+ cells. Thus, our results demonstrate that AngII and its receptor signaling play a role in nanoparticles-induced pulmonary injury, and serum VEGF and ICAM-1 may serve as an indicator of pulmonary injury upon exposure.

張志欽、林洺秀: 以動物實驗驗證奈米微粒至肺損傷之健康危害。行政院勞工委員會勞工安全衛生研究所2014年1月。
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