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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林思洸 | zh_TW |
| dc.contributor.advisor | Sze-Kwan Lin | en |
| dc.contributor.author | 何欣庭 | zh_TW |
| dc.contributor.author | Hsin-Ting Ho | en |
| dc.date.accessioned | 2024-08-28T16:13:30Z | - |
| dc.date.available | 2024-08-29 | - |
| dc.date.copyright | 2024-08-28 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-23 | - |
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Regardh, Clinical pharmacokinetics of felodipine. A summary. Drugs, 1987. 34 Suppl 3: p. 16-27. 64. Xing, S.S., et al., Felodipine reduces cardiac expression of IL-18 and perivascular fibrosis in fructose-fed rats. Mol Med, 2008. 14(7-8): p. 395-402. 65. Qi, J., et al., Felodipine inhibits ox-LDL-induced reactive oxygen species production and inflammation in human umbilical vein endothelial cells. Mol Med Rep, 2017. 16(4): p. 4871-4878. 66. Swain, R., et al., Ocular delivery of felodipine for the management of intraocular pressure and inflammation: Effect of film plasticizer and in vitro in vivo evaluation. Int J Pharm, 2023. 642: p. 123153. 67. Kou, L., et al., Biomaterial-engineered intra-articular drug delivery systems for osteoarthritis therapy. Drug Deliv, 2019. 26(1): p. 870-885. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95092 | - |
| dc.description.abstract | 根尖病變主要是由於牙髓腔的細菌感染所引起的根尖周圍組織發炎反應，宿主組織在修復時會產生抑制和刺激訊號的複雜交互作用，影響根尖病變的病程發展。
27-羥基膽固醇(27-hydroxycholesterol, 27-HC)是人體內含量最高的羥基膽固醇，也是一種內生性的選擇性雌激素受體調節劑，在停經和高膽固醇血症引起的發炎反應中扮演關鍵角色。我們以巨噬細胞株的實驗證實：當鈣離子濃度改變下，原本存在於細胞質中的類固醇生成急性調控蛋白(steroidogenic acute regulatory protein, StAR)會轉移到粒線體外膜上，使膽固醇能夠進入粒線體基質，與固醇27-羥化酶(CYP27A1)作用生成27-HC。 長期用於治療高血壓的felodipine，經研究證實可以抑制CYP27A1這個酵素。而作為一種鈣離子通道阻斷劑，我們以巨噬細胞株的實驗驗證：felodipine透過抑制鈣離子通道，影響細胞內鈣離子的濃度和轉移，減少StAR蛋白從細胞質轉移到粒線體外膜的量，進而降低膽固醇進入粒線體內部，最後使27-HC生成量下降。使用大鼠作為研究動物的實驗，分成有服用felodipine與對照組的組別，對於有使用felodipine的組別，根尖病變的發炎狀況有改善。結果顯示felodipine應用於臨床上的潛能，也許可以做成奈米藥物後注射至發炎的位置，來達成抑制發炎的效果，同時也比較不會產生全身性的影響。 | zh_TW |
| dc.description.abstract | Periapical lesion is an inflammatory reaction in the periapical tissue caused by the bacterial infection in the pulp chamber. Complex inhibitory and stimulatory signals of the host during the healing process affect the progression of the periapical lesion.
27-hydroxycholesterol (27-HC) are the most abundant oxysterol in humans and an endogenous selective estrogen receptor modulator (SERM), playing a key role in the inflammatory response induced by menopause and hypercholesterolemia. According to our experiments with macrophage cell lines, it has confirmed that when the calcium ion concentration changes, the steroidogenic acute regulatory protein (StAR) originally present in the cytoplasm translocates to outer membrane of mitochondria. After the cholesterol enters the mitochondrial matrix, it interacts with the sterol 27-hydroxylase (CYP27A1) to produce 27-HC. Felodipine, a long-standing drug for treating hypertension, has been shown to inhibit the enzyme CYP27A1. As a calcium channel blocker, our in vitro experiments with macrophage cell lines have verified that felodipine, by block the entry of the extracellular calcium ions, reduces the translocation of StAR protein from cytoplasm to the outer membrane of the mitochondria. Therefore, it decreases the movement of cholesterol into the mitochondria and ultimately reduces the production of 27-HC. In our animal study with rats, the inflammation of the periapical lesion improved in the felodipine-treated group compared with the control group. Perhaps in the form of a nanoparticle drug injected into the site of inflammation, felodipine might achieve an anti-inflammatory effect without causing systemic effects. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-28T16:13:30Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-28T16:13:30Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
中文摘要 ii 英文摘要 iii 圖次 viii 表次 ix 第一章 導論 1 1.1 根尖病變 1 1.2 停經 1 1.2.1 雌激素與其受體 1 1.2.2 選擇性雌激素受體調節劑 2 1.2.3 雌激素與免疫反應 2 1.2.4 雌激素與骨吸收 3 1.3 高膽固醇血症 4 1.3.1 膽固醇的功能 4 1.3.2 膽固醇的代謝 4 1.3.3 膽固醇與免疫反應 5 1.4 27-羥基膽固醇 5 1.4.1 27-羥基膽固醇與類固醇生成急性調控蛋白 6 1.4.2 27-羥基膽固醇與免疫反應 6 1.5 Felodipine 6 第二章 實驗目的 8 第三章 材料與方法 10 3.1 實驗細胞株 10 3.1.1 J774細胞 10 3.1.2 BMDM (bone-marrow-derived macrophage) 10 3.2 西方點墨法(Western blot) 11 3.2.1 細胞內蛋白質萃取 12 3.2.2 細胞粒腺體/細胞質蛋白質萃取 12 3.2.3 蛋白質的定量 12 3.3 酵素免疫分析法(enzyme-linked immunosorbent assay, ELISA) 13 3.3.1 27-羥基膽固醇濃度檢測 13 3.4 Filipin和MitoTracker Red的共定位(colocalization) 14 3.5 誘導根尖病變之動物實驗 15 3.5.1 誘導根尖病變之形成 15 3.5.2 Felodipine藥物投予 15 3.5.3 動物犧牲與檢體製備 16 3.5.4 微型電腦斷層掃描 16 3.5.5 切片的製備與染色 16 3.6 統計分析方法 18 第四章 實驗結果 19 4.1膽固醇對巨噬細胞內27-HC生成量的影響 19 4.1.1膽固醇的濃度與27-HC生成量 19 4.1.2膽固醇與27-HC生成的時間 19 4.2巨噬細胞粒腺體內膽固醇生成27-HC的機制 19 4.2.1膽固醇與StAR移動至粒腺體的量 19 4.2.2膽固醇進入粒線體的量 19 4.2.3 StAR的量與27-HC的生成 20 4.2.4鈣離子影響StAR移動與27-HC的生成量 20 4.3巨噬細胞內27-HC與發炎反應 21 4.3.1 細胞內27-HC與CCL20的生成 21 4.4 Felodipine對巨噬細胞內27-HC生成量的影響 21 4.4.1 Felodipine對StAR的影響 21 4.4.2 Felodipine對膽固醇進入粒線體量的影響 21 4.4.2 Felodipine對27-HC生成量的影響 22 4.5 Felodipine對停經與高膽固醇血症惡化根尖病變進程的影響 22 4.5.1 Felodipine對血液中膽固醇與27-HC含量的影響 22 4.5.2 Felodipine對停經與高膽固醇血症惡化根尖病變的變化 22 第五章 討論 24 5.1 停經、高膽固醇血症與發炎反應 24 5.1.1 停經、高膽固醇血症與27-HC 24 5.1.2 27-HC與發炎反應 25 5.2 巨噬細胞27-HC的形成機制 25 5.2.2 鈣離子與StAR 26 5.3 抑制的27-HC所誘發的發炎反應與Felodipine 27 5.3.1 Felodipine抑制27-HC的機制 28 5.3.2 Felodipine可能具有減緩根尖病變進程的效果 28 參考文獻 30 附錄 35 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 非洛地平 | zh_TW |
| dc.subject | 27-羥基膽固醇 | zh_TW |
| dc.subject | 類固醇生成急性調控蛋白 | zh_TW |
| dc.subject | 停經 | zh_TW |
| dc.subject | 根尖病變 | zh_TW |
| dc.subject | 高膽固醇血症 | zh_TW |
| dc.subject | Felodipine | en |
| dc.subject | periapical lesion | en |
| dc.subject | menopause | en |
| dc.subject | hypercholesterolemia | en |
| dc.subject | 27-hydroxycholesterol | en |
| dc.subject | StAR | en |
| dc.title | Felodipine減緩高膽固醇血症與停經狀態下 根尖病變的惡化 | zh_TW |
| dc.title | Felodipine attenuates periapical lesion exacerbation on individuals under hypercholesterolemia and post-menopausal status | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 郭生興;洪志遠 | zh_TW |
| dc.contributor.oralexamcommittee | Sang-Heng Kok;Chi-Yuan Hong | en |
| dc.subject.keyword | 根尖病變,停經,高膽固醇血症,27-羥基膽固醇,類固醇生成急性調控蛋白,非洛地平, | zh_TW |
| dc.subject.keyword | periapical lesion,menopause,hypercholesterolemia,27-hydroxycholesterol,StAR,Felodipine, | en |
| dc.relation.page | 49 | - |
| dc.identifier.doi | 10.6342/NTU202401979 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-07-23 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 臨床牙醫學研究所 | - |
| dc.date.embargo-lift | 2029-07-19 | - |
| 顯示於系所單位： | 臨床牙醫學研究所 | |
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