Title

利用小鼠動物模式探討克弗爾肽減緩空氣懸浮微粒 (PM4.0) 誘發之急性肺發炎反應

Translated Titles

Kefir peptides alleviate particulate matter (PM4.0)-induced acute lung inflammation in mouse model.

Authors

洪冠妃

Key Words

空氣懸浮微粒 ; 急性肺發炎 ; 生物活體影像 ; 克弗爾肽 ; Particulates matter ; Acute lung inflammation ; Non Invasion In Vivo Imaging System ; Kefir peptides

PublicationName

中興大學生命科學系所學位論文

Volume or Term/Year and Month of Publication

2018年

Academic Degree Category

碩士

Advisor

陳全木

Content Language

繁體中文

Chinese Abstract

近年來的空氣汙染日益嚴重,而造成空氣污染的主因為空氣懸浮微粒 (particulate matter,PM),空氣懸浮微粒又分成許多不同的粒徑,粒徑的大小會影響其堆積在支氣管到肺泡的位置導致不同程度肺發炎,甚至有些會擴散至血液中到達其他器官,間接地造成不同疾病產生,最為顯著的是呼吸道及心血管疾病。目前市面上常用來治療肺發炎的藥物多為抗生素,但濫用抗生素會使細菌產生抗藥性,且「預防勝於治療」。由本實驗室自行開發的克弗爾肽(Kefir peptides),其有調節免疫系統的功效,將此胜肽作為預防保健食品,並進一步探討是否能有效改善肺組織及全身性的發炎。本實驗以粒徑小於4 μm之空氣懸浮微粒(PM 4.0)來誘導八週齡大的發炎誘導性冷光基因轉殖鼠(NF-κB/Luc.)產生急性肺發炎,當小鼠身體有發炎時,利用生物活體影像的操作便可即時且準確觀察到發炎的部位。研究中首先成功建立每日利用氣管滴注PM4.0誘導肺發炎之小鼠模式;接著再以預防性給藥之方式,即在每日給予PM4.0前,利用管餵的方式給予克弗爾肽,於四週後犧牲小鼠,從肺泡沖洗液(BALF)的檢測結果,顯示活性氧化物的表現量有減少;肺泡浸潤的免疫細胞有明顯減少,其中包括巨噬細胞與嗜中性白血球;IL-1β、TNF-α之發炎相關蛋白量也有明顯減少,而肺組織的發炎因子包括p-NF-κB、NLRP3、Caspase-1、IL-6、IL-1β、TNF-α其表現量也是明顯減少;從組織切片觀察到發炎及纖維化的程度有明顯下降;生物活體影像分析亦顯示克弗爾肽有明顯降低肺發炎情形,綜合以上結果可得知克弗爾肽作為預防保健食品能有效改善由空氣懸浮微粒所誘導的肺發炎,也推測出其透過降低活化NF-κB路徑的方式來減緩發炎。本實驗未來若能進一步於人體試食試驗作驗證,將有助於應用在人體的健康保健,使大家都能遠離空氣懸浮微粒的危害。 關鍵字:空氣懸浮微粒、急性肺發炎、生物活體影像、克弗爾肽

English Abstract

In recent years, the air pollution is getting worse day by day. The major concern of air pollution is particulate matter (PM). Particulate matters are divided into many different aerodynamic diameter, which affect the accumulation of bronchial to alveolar leading to different degrees of lung inflammation. And some will spread to the blood to reach other organs resulting in different diseases indirectly. The most significant symptoms are respiratory and cardiovascular diseases. Antibiotics often used to treat pulmonary inflammation on the market currently, but the abuse of antibiotics will make bacteria resistant. And "prevention is better than cure". Kefir peptides is generated by kefir grain fermentation from milk proteins by our laboratory, which have regulate the function of the immune system. We use kefir peptides as a preventive food, and further investigated whether it can effectively improve lung and systemic circulation inflammation. In our experiment, particulate matter (PM 4.0) with aerodynamic diameter less than 4 μm were used to induce acute inflammation of the lung in an eight-week-old inflammation-inducing luminescence gene transgenic mouse (NF-κB / Luc.). The use of biological living images can be immediately and accurately observed the inflammation sites. First of all, we successfully established a mouse model of pulmonary inflammation that induced by PM4.0 through intratracheal instillation after the kefir peptide administration. Mice were sacrificed until finish four weeks experiment. The results from the alveolar washing fluid (BALF) showed a decrease in the amount of reactive oxygen species; alveolar infiltration of immune cells were significantly reduced, including macrophages and neutrophils ; The inflammation-related protein levels of IL-1β and TNF-α also decreased significantly. The expression of inflammatory proteins in lung tissue including p-NF-κB, NLRP3, Caspase-1, IL-6, IL-1β, TNF-α also significantly reduced. The tissue sections showed the degree of inflammation and fibrosis are significantly decreased. Biological living images results also showed that kefir peptides significantly reduced lung inflammation. In summary, kefir peptides as a preventive foods are effective in improving lung inflammation induced by particulate matter and also presumed kefir peptides reduce inflammation through inhibiting NF-κB pathway. We hoped that the results of our experiment can be further validated by human study and applied to the health and well-being of human beings in the future so that everyone can get away from the harmful effects of particulate matter. Keywords:Particulates matter, Acute lung inflammation, Non Invasion In Vivo Imaging System, Kefir peptides

Topic Category 生命科學院 > 生命科學系所
生物農學 > 生物科學
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