急性肺損傷 (Acute lung injury, ALI) 是一個無論在嬰兒或成人身上都有很高發病率與死亡率的疾病，這個疾病會使肺臟產生非常嚴重的發炎反應，而發生的原因通常都是局部性的肺炎與全身性的敗血症。這疾病可區分為三個階段：免疫細胞浸潤期、組織修補的增生期、增生異常而導致纖維化。特異性肺纖維化 (Idiopathic pulmonary fibrosis, IPF) 是一個慢性且致死率非常高的肺纖維化疾病，到目前為止特異性肺纖維化的發病原因還是未知的。然而這兩種疾病有一個共同的病理症狀，就是會造成低血氧症與呼吸衰竭。肺泡表面蛋白質D (Surfactant protein D, SP-D) 是屬於C-type lectin的一員，而且是由肺泡第二型上皮細胞所分泌的，並且在呼吸性統的先天免疫與抗發炎上扮演重要的角色，SP-D在這兩個疾病中扮演什麼作用到現在並不清楚。因此本研究中想利用博萊黴素 (bleomycin) 所誘導的肺纖維化動物模式來探討SP-D的功能。Bleomycin原本是個化學的抗癌藥物，在使用過後會產生過多得活化自由基，竟而產生不可逆轉的肺損傷，所以在這動物模式中我們可以看到第14天時，老鼠的肺功能狀況最差，並且產生最多發炎的細胞激素，如介白素-6 (Interleukin 6, IL-6) 和一氧化氮 (Nitric oxide, NO) 與會導致纖維化的細胞激素：轉化生長因子-β1 (Transforming growth factor-β1, TGF-β1)，在病理切片上一樣可以觀察到肺泡的空間被膠原蛋白所填滿，而這個現象與人類的病理切片相似。為了觀察SP-D是否有影響，所以我們先進行ex vivo的實驗，結果發現無論是重組的或是天然的SP-D都能很明顯地去抑制發炎細胞激素的表現，最後進行in vivo的實驗，同樣發現給予SP-D的小鼠在bleomycin所誘導肺纖維化中體重與肺功能有明顯的恢復，並且也能使轉化生長因子-1 與一氧化氮的表現量下降。因此我們能說SP-D同時具有抗發炎與抗纖維化的能力在ALI與IPF中，故SP-D有可能在未來成為醫治ALI與IPF的新治療藥物。

Acute lung injury (ALI), which is associated with a high mortality and morbidity in both infants and adults, is caused by severe lung inflammation resulted from a variety of local and systemic infection such as sepsis and pneumonia. According to the disease procession, there are three stages: exudate formation, proliferation, and fibrosis. Idiopathic pulmonary fibrosis (IPF) is another chronic, progressive and lethal fibrotic lung disease. The etiology of IPF is still unknown. However, both diseases have some similar hallmarks such as hypoxemia and respiratory failure. Surfactant protein D (SP-D), a C-type lectin, which is produced by alveolar type II cells, is important on respiratory innate immunity and anti-inflammation. The action of SP-D in these diseases is still unrevealed. In this study, we used bleomycin to induce the animal model of ALI and IPF. Bleomycin is a chemotherapeutic antibiotic drug clinically used in lymphoma and squamous cell carcinomas, but the following overproduction of reactive oxygen can lead to irreversible lung injury. In this animal model, we have found that 14-day-course was the group presenting the most severe resistance and the poorest elastance of lung tissue. In addition, the pro-inflammatory cytokines (interleukin-6, interleukin-17, tumor necrosis factor-α, interferon-γ and nitric oxide) were followed by increased expression of pro-fibrotic cytokines (transforming growth factor-β1). The histological alterations caused by bleomycin such as mural incorporation of collagen and obliteration of the alveolar space are similar to human IPF. In ex vivo study, pretreatment with recombinant human SP-D or native SP-D can significantly decrease the production of pro-inflammatory cytokines. In in vivo study, treatment with native SP-D in bleomycin-induced lung fibrosis in mice also showed significant body weight increase, recovery of lung function, decline of the production of transforming growth factor-β1 (TGF-β1) and nitric oxide. Therefore, we conclude that SP-D may have prominent anti-inflammatory and anti-fibrotic effects on ALI and IPF, and also have the potential to become a novel treatment of ALI and IPF in the near future.

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