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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳玉怜(Yuh-Lien Chen) | |
dc.contributor.author | Hui-Hua Cheng | en |
dc.contributor.author | 程卉華 | zh_TW |
dc.date.accessioned | 2021-06-17T07:01:11Z | - |
dc.date.available | 2022-08-26 | |
dc.date.copyright | 2019-08-26 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-01 | |
dc.identifier.citation | Adams, J. S., and Hewison, M. (2012). Extrarenal Expression of the 25-Hydroxyvitamin D-1-Hydroxylase. Arch Biochem Biophys, 523(1), 95-102.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72574 | - |
dc.description.abstract | 近年來,空氣污染已逐漸成為全世界關注的公共衛生問題。空氣中的懸浮微粒 (Particulate matter, PM2.5)直徑小於2.5 μm,容易進入呼吸道深處並參與全身血液循環,使得生物體內各種不良反應的產生。因此,PM2.5對人體健康的影響已成為一個重要的議題。流行病學研究顯示,PM2.5會導致心血管、肺癌等疾病的發生,且可能誘導氧化壓力的產生、發炎反應,內皮細胞功能障礙等。空氣汙染是糖尿病發生率增加的原因之一,但仍需更多研究加以闡明。在本實驗中,我們以30 mM葡萄糖與50 μg/ml的PM2.5處理人類臍靜脈內皮細胞 (Human umbilical vein endothelial cells, HUVECs )模擬高糖與空氣污染之環境。實驗結果顯示,PM2.5會促使高糖處理的細胞存活率顯著性的下降,也會使細胞凋亡的現象增加。在此處理下還可觀察到活性氧化物 (reactive oxygen species, ROS)的含量上升、清除ROS的酵素- SOD1 (superoxide dismutase 1)的蛋白表現量下降。另外,也會使粒線體膜電位下降、自噬小體的形成、粒線體自噬相關蛋白p62、LC3B (microtubule-associated protein 1 light chain 3 beta)、Bnip3 (BCL2 Interacting Protein 3)及透過MAPKs (mitogen-activated protein kinases)這條訊息傳遞路徑使發炎相關蛋白ICAM-1 (intracellular adhesion molecule-1)及VCAM-1 (vascular cell adhesion protein 1)的表現上升。而加入維他命D處理後,可以透過降低ROS生成而使細胞存活率回升、降低粒線體自噬與發炎現象而達到保護內皮的效果。動物實驗部分,我們以STZ (streptozotocin)誘導小鼠使其產生高血糖,以氣管內注射(intratracheal instillation) PM模擬暴露空氣污染之環境。結果顯示,暴露PM2.5的糖尿病小鼠其胸主動脈之ROS含量有增加的現象,而VCAM-1, p62及Bnip3的蛋白表現量也有上升的趨勢;而給予維他命D處理則可以減少此現象。透過本篇實驗,我們了解懸浮微粒在高糖環境下增加細胞內氧化壓力、粒線體自噬及發炎現象,而維他命D可以透過降低ROS生成而達到保護內皮細胞之效果。 | zh_TW |
dc.description.abstract | Environmental particulate matter 2.5 (PM2.5) can penetrate deep into the respiratory tract, reach the alveolar region, participate in blood circulation, and is associated with the development of lung cancer and cardiovascular diseases. It may also promote inflammation, oxidative stress and endothelial dysfunction. Air pollution has been found to be one of the risk factors for diabetes, but evidence is limited. Here, we treated human umbilical vein endothelial cells (HUVECs) with 30 mM glucose and 50 μg/ml PM (HG + PM) to mimic endothelial cells under hyperglycemia and air pollution. First, we demonstrated that HUVECs exposed to PM in a high glucose (HG) environment showed a significant increase in cell damage and apoptosis. In addition, PM significantly increased reactive oxygen species (ROS) production in HG-treated HUVECs. The expression of superoxide dismutase 1 (SOD1), an enzyme of ROS scavenger, was also reduced. Using the JC-1 assay and MitoStatus staining to examine mitochondrial membrane potential, we demonstrated that mitochondrial membrane potential tends to collapse in the PM and HG + PM groups. We also showed that high glucose and PM can induce the formation of autolysosomes in HUVECs by acridine orange (AO) staining. Proteins associated with mitochondrial autophagy, p62, microtubule-associated protein 1 light chain 3β (LC3B) and BCL2 interacting protein 3 (Bnip3), were increased in the PM and HG + PM group compared to the control and HG group. In addition, autophagosome-like structures were observed in the HG + PM group by transmission electron microscopy. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were also increased through JNK/p38 signaling pathway in the HG + PM group. Furthermore, we investigated whether vitamin D protects HUVECs under high glucose and PM conditions. Endothelial cells pretreated with vitamin D significantly increased cell viability and reduced mitochondrial ROS production under high glucose and PM conditions. Vitamin D also reduced the formation of autolysosomes using AO staining. The levels of p62, LC3B, Bnip3, ICAM-1 and VCAM-1 expression were decreased after vitamin D treatment. In addition, we used streptozotocin (STZ)-induced diabetic mice as an animal model. Mice were treated with PM by intratracheal instillation. The aortas of the HG + PM group showed increased ROS production by DHE staining and increased levels of VCAM-1, p62, and Bnip3 by Western blot; while vitamin D could reverse these phenomena. Taking together, these results suggested that PM exerted the enhancement of cell injury under high glucose environment via ROS production, mitophagy and inflammation, and vitamin D could protect HUVECs against these phenomena by suppressing oxidative stress. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:01:11Z (GMT). No. of bitstreams: 1 ntu-108-R06446001-1.pdf: 7585109 bytes, checksum: bf554a5c61598f13257945e34a223bba (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員審定書 ii
致謝 iii 摘要 iv Abstract vi Contents viii Chapter 1. Introduction 1 1. Particulate matter and cardiovascular diseases 1 2. Diabetes and cardiovascular diseases 2 3. The relationship between particulate matter and diabetes 3 4. The role of endothelial cells in cardiovascular diseases 4 5. The role of reactive oxygen species (ROS) in the effects under PM or high glucose treatment 5 6. The relationship between endothelial dysfunction and inflammation 6 7. Autophagy 9 8. Mitophagy 11 9. Vitamin D3 14 10. Aims 16 Chapter 2. Materials 18 1. Instrument 18 2. Materials and reagents 20 3. Solution 25 Chapter 3. Methods 28 1. Preparation of PM 28 2. Cell culture 28 3. Cell culture and treatment 29 4. Cell viability assay 30 5. Annexin V/PI assay 31 6. Analysis of mitochondrial ROS and cellular ROS levels 31 7. Measurement of mitochondrial transmembrane potential 32 8. Western blot analysis 33 9. Acridine orange staining 36 10. Transmission electron microscope 36 11. ELISA (Enzyme-Linked Immunosorbent Assay) 37 12. Animal model 38 13. Paraffin embedding 38 14. ROS Measurement of aortas 39 15. Statistical analysis 39 Chapter 4. Results 40 Chapter 5. Discussion 49 Chapter 6. References 55 Chapter 7. Figures 70 | |
dc.language.iso | en | |
dc.title | 探討懸浮微粒透過粒線體自噬影響高糖處理內皮細胞之發炎 | zh_TW |
dc.title | To study the effects of particulate matter on
the inflammation of high glucose-treated endothelial cells through mitophagy | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 江美治(Meei-Jyh Jiang),王懷詩(Hwai-Shi Wang),李宗玄(Tzong-Shyuan Lee),吳佳慶(Chia-Ching Wu) | |
dc.subject.keyword | 懸浮微粒,糖尿病,內皮功能障礙,活性氧化物,粒線體自噬,發炎反應,維他命D3, | zh_TW |
dc.subject.keyword | Particulate matter,Diabetes,Endothelial dysfunction,ROS,mitophagy,Inflammation,Vitamin D3, | en |
dc.relation.page | 84 | |
dc.identifier.doi | 10.6342/NTU201902350 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-08-01 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
顯示於系所單位: | 解剖學暨細胞生物學科所 |
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