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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭生興(Sang-Heng Kok) | |
| dc.contributor.author | Ying-Hong Chen | en |
| dc.contributor.author | 陳盈宏 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:07:44Z | - |
| dc.date.copyright | 2022-06-23 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-06-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84283 | - |
| dc.description.abstract | 研究背景 牙周疾病是世界口腔疾病中發生率僅次於蛀牙的疾病，在台灣有高達99.2%的成人有程度不一的牙周病。肥胖讓身體呈現慢性低度的發炎，導致巨噬細胞浸潤，如同牙周病一般。停經會增加骨質疏鬆的發生率，和牙周病都是骨頭代謝疾病。肥胖與停經都已經證實會增加牙周病發病率，但相關的機制卻尚未清楚了解，因此本論文主要研究膽固醇代謝產物27-hydroxycholesterol (27HC)對於停經與肥胖狀態下牙周病的致病機轉，以及骨質疏鬆症藥物Raloxifene對於牙周病治療之潛能。 研究方法 利用J774細胞實驗與大鼠牙周誘導實驗搭配肥胖與停經模擬，探討27HC和Raloxifene對於牙周疾病之影響。 結果 細胞實驗結果顯示膽固醇能夠透過27HC刺激J774細胞內CCL2及COX-2發炎因子的表現，而牙周發炎區域的促發炎因子TNF-α具有加強27HC的生成。給予Raloxifene後，J774細胞內的CCL2及COX-2則會顯著下降。動物實驗方面，高脂飼料或卵巢摘除手術的大鼠，其血清膽固醇會顯著上升，但對血清27HC沒有影響。當兩個因子合併時，肝臟27HC與牙齦27HC的表現有上升的趨勢，並對齒槽骨破壞達顯著上的差異。而給予Raloxifene的大鼠組別，非酒精性脂肪肝病活性指數(NAFLD activity score, NAS)有下降趨勢，對於齒槽骨破壞也會有顯著的降低。 總結 本研究嘗試以27HC來闡述肥胖與停經對牙周病的影響，雖然有相關的趨勢存在，但詳細的機制還需要進一步的研究。而實驗的結果顯示Raloxifene未來具有發展成牙周病治療輔助藥物之潛能。 | zh_TW |
| dc.description.abstract | Background Periodontal disease is the second most common oral disease in the world after tooth decay. In Taiwan, up to 99.2% of adults have periodontal disease of varying degrees, and the treatment and subsequent rehabilitation cost occupy a great deal of National Health Insurance and social resources. Obesity presents chronic low-grade inflammation in the body, leading to infiltration of macrophages, as in periodontal disease. Menopause increases the incidence of osteoporosis and is a metabolic disease of the bonelike periodontal disease. Both obesity and menopause have been proven to promote the periodontal disease, but the relevant mechanisms are not yet clearly understood. Therefore, this research mainly focuses on the effect of cholesterol metabolite 27-hydroxycholesterol (27HC) on the progression of periodontal disease in postmenopausal and obese status and the mechanism and therapeutic potential of Raloxifene, a drug for the prevention and treatment of osteoporosis, for periodontal disease. Method Using J774 cell line and periodontitis induction experiment in vivo with obesity and menopause simulation to explore the effect of 27HC and Raloxifene on periodontal disease. Result The results showed that the level of proinflammatory cytokine CCL2 and COX-2can be stimulated by 27HCin J774cell and TNF-α which is common in inflamed periodontal tissue enhanced more 27HC production. Oppositely, Raloxifene dropped CCL2 and COX-2 significantly. In animal model, high fat diet and ovariectomy caused the obvious elevation of serum cholesterol but no change in serum 27HC. Combination of obesity and menopause leaded to the trend of increasing 27HC in liver and gingiva and promoted the alveolar bone destruction. While the group given Raloxifene showed a downward trend for non-alcoholic fatty liver disease activity score(NAS) and alleviated the alveolar bone destruction statically. Conclusion This study attempts to elucidate the effect of obesity and menopause on periodontal disease through 27HC. Although it may be relevant, the mechanism needs more research to uncover. The results show that Raloxifene has the potential to be an adjuvant drug for periodontal disease treatment in the future. | en |
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| dc.description.tableofcontents | 誌謝 I 中文摘要 II Abstract III 圖目錄 VIII 表目錄 IX 第一章 導論 1 1.1 牙周病 1 1.2 停經與疾病 1 1.3 肥胖與疾病 2 1.4 27-烴基膽固醇(27-hydroxycholesterol, 27 HC) 3 1.5 Cyclooxygenase-2 (COX-2) 3 1.6 Chemokine (C-C motif) ligand 2 (CCL2) 4 1.7 Tumor necrosis factor-alpha (TNF-α) 4 1.8 Raloxifene 5 1.9 非酒精性脂肪肝病(NAFLD) 5 第二章 研究動機與目的 7 2.1 研究動機 7 2.2 研究目的 9 第三章 材料與方法 10 3.1 實驗細胞株 10 3.1.1 J774細胞株 10 3.1.2 膽固醇 10 3.1.3 27-烴基膽固醇(27-hydroxycholesterol, 27HC) 10 3.1.4 TNF-α 10 3.2 蛋白質萃取及定量 11 3.2.1 Total cell lysis 11 3.2.2 Tissue cell lysis 11 3.2.3 蛋白質定量 11 3.3 西方點墨法(Western blot) 12 3.4 酵素結合免疫吸附分析法(ELISA) 13 3.4.1 27-烴基膽固醇(27-hydroxycholesterol, 27HC)濃度檢測 13 3.4.2 CCL2 (Chemokine (C-C motif) ligand 2)濃度檢測 14 3.5 膽固醇濃度檢測 14 3.6 大鼠牙周病誘導實驗 14 3.6.1 Sprague Dawley大鼠 14 3.6.2 動物停經因子模擬 15 3.6.3 動物肥胖因子模擬 15 3.6.4 牙周疾病誘導手術 15 3.6.5 Raloxifene藥物投予 16 3.6.6 組織檢體採集 16 3.7 免疫組織化學染色(Immunohistochemistry) 17 3.8 蘇木精-伊紅染色(Hematoxylin and eosin stain ) 18 3.9 微型電腦斷層掃描(Micro computed tomography) 18 3.10 非酒精性脂肪肝病活性指數(NAFLD activity score, NAS) 18 3.11 牙周發炎得分系統(Inflammation scoring system for periodontal status) 19 第四章 實驗結果 20 4.1膽固醇具有刺激J774細胞內27HC的生成 20 4.2 27HC能刺激J774細胞發炎反應 20 4.3 Raloxifene具有降低27HC引起之發炎反應 20 4.4停經會導致體重上升 21 4.5 卵巢摘除手術對血清膽固醇及27HC濃度的影響 21 4.6 肥胖合併停經對肝臟27HC有增加趨勢且影響肝臟組織發炎程度 22 4.7 肥胖與停經影響局部牙齦發炎部位27HC濃度之表現 22 4.8 在動物模式中肥胖與停經對牙周疾病之影響 23 第五章 討論 25 參考文獻 31 圖目錄 圖 1、大鼠於上顎第一大臼齒及第二大臼齒間進行牙周病誘導 39 圖 2、膽固醇促進J774細胞內27HC生成 40 圖 3、27HC在24小時後能刺激J774細胞產生CCL2 41 圖 4、27HC活化J774細胞內COX-2的表現 42 圖 5、Raloxifene (Ralo)能夠降低27HC對J774細胞促進CCL2生成的效果 43 圖 6、Raloxifene能夠抑制27HC對J774細胞產生COX-2的效果 44 圖 7、大鼠體重與飼養週數之趨勢圖 45 圖 8、各組大鼠在飼養第8週的平均體重 46 圖 9、高脂飼料及卵巢摘除手術有增加血清膽固醇(CHL)的趨勢 47 圖 10、各組大鼠血清中平均27HC 48 圖 11、肝臟27HC濃度在高脂肪飼料合併卵巢摘除手術中有上升趨勢 49 圖 12、肝臟組織切片於200倍放大下NAFLD activity score之組織學特徵 50 圖 13、各組大鼠肝臟組織切片NAFLD activity score (NAS) 51 圖 14、各組發炎區域牙齦27HC平均含量 52 圖 15、上顎第一大臼齒及第二大臼齒電腦斷層矢狀切面 53 圖 16、牙周炎齒槽骨喪失計算方法 54 圖 17、各組動物齒槽骨喪失比率 55 圖 18、各組第一大臼齒及第二大臼齒之間牙周組織染色圖 56 圖 19、牙周組織發炎程度periodontitis score統計 58 表目錄 表 1、各組大鼠最高和最低體重個體列表及差距 59 | |
| dc.language.iso | zh-TW | |
| dc.title | Raloxifene減緩肥胖與停經狀態下牙周疾病進展:作用機轉與治療潛能 | zh_TW |
| dc.title | Raloxifene alleviates progression of periodontal disease in menopause and obesity status: mechanism and therapeutic potential | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 林思洸(Sze-Kwan Lin) | |
| dc.contributor.oralexamcommittee | 洪志遠(Chi-Yuan Hong) | |
| dc.subject.keyword | 牙周病,肥胖,停經,27HC,Raloxifene, | zh_TW |
| dc.subject.keyword | periodontitis,obesity,menopause,27HC,raloxifene, | en |
| dc.relation.page | 59 | |
| dc.identifier.doi | 10.6342/NTU202200991 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-06-20 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2027-06-17 | - |
| 顯示於系所單位： | 臨床牙醫學研究所 | |
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