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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 郭彥彬 | |
| dc.contributor.author | Chun-Ling Wang | en |
| dc.contributor.author | 王淳鈴 | zh_TW |
| dc.date.accessioned | 2021-06-17T02:38:07Z | - |
| dc.date.available | 2020-09-12 | |
| dc.date.copyright | 2017-09-12 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68842 | - |
| dc.description.abstract | Phenytoin是一種常見用來治療癲癇的藥物，但常會造成服用此藥的病人產生牙齦過度增生(Gingival overgrowth，GO)，進而影響到病患的說話、吞嚥、咀嚼、口腔衛生、美觀等生活上的基本功能，而無法有好的生活品質。現在治療GO主要的方式是經由手術切除，但再復發率高。許多研究指出上皮-間質轉換(epithelial-mesenchymal transition，EMT)的進程發生在受傷組織癒合、腫瘤轉移、器官纖維化，而轉型生長因子-β1(Transforming growth factor-1，TGF-β1) )可誘導EMT的現象並且在牙齦過度生長、纖維化等疾病中扮演重要角色。本研究中發現人類牙齦表皮OECM-1和Ca9-22細胞株在處理phenytoin 48小時後，有上皮鈣黏蛋白(E-cadherin)表現量下降，和神經鈣黏蛋白(N-cadherin)表現量上升的EMT現象。phenytoin 可誘導OECM-1和Ca9-22的p-Smad3的表現。以TGF-β1的中和抗體、ALK5的抑制劑SB431542前處理後皆可抑制phenytoin 誘導的p-Smad3的表現，顯示Phenytoin可誘導TGF-β1的訊息傳遞路徑。ELISA分析中發現Phenytoin會使細胞培養液中活化態的TGF-β增加。前處理抗氧化劑N-acetyl-cystenine (ROS抑制劑)、Diphenylene iodonium (NOX抑制劑)、Plumbagin (NOX4抑制劑)、Apocynine (NOX2抑制劑)可以抑制phenytoin誘導的活化態TGF-β產生。表示TGF-β的活化可能是經由NOX2、NOX4 產生的 ROS。另外我們也發現常見天然食品中的成分薑黃素 (Curcumin)可抑制OECM中Phenytoin所誘導的p-Smad3的表現和活化態TGF-β1的釋放，進而抑制TGF-β1下游的訊息傳遞。冀望未來薑黃素可以成為治療或預防GO的潛力藥物。 | zh_TW |
| dc.description.abstract | Gingivl overgrowth ( GO ) is a common complication of the usage of phenytoin. It causes severe adverse effect in life quality of patient in maintenance of oral hygiene, language and swallowing.
Clinically, periodontal therapy offers removal of the inflammatory component of the GO through scaling and gingival curettage followed by surgical interventions. However, the high recurrence rate of drug-induced gingival overgrowth requires gingivectomy must be repeated periodically. Transforming growth factor β ( TGF-β) is a key regulator associated with pathogenesis of GO. Epithelial-mesenchymal transition (EMT) occurs in wound healing, tumor metastasis and fibrosis. In this study , we found that after 48 hours treatment with phenytoin, the expression of E-cadherin decreased； N-cadherin , vimentin and slug increased in the human gingival epithelial cell (OECM-1,CA9-22) . Pretreatment with TGF-β1 neutralizing antibody, ALK5 in inhibitor SB431542 significantly reduced phenytoin induced p-Smad3 protein production. Furthermore, we found phenytoin increased activated TGF-β levels in OECM-1and CA9-22.Pretreatment of N-acetyl-cystenine ( ROS inhibitor), Diphenylene iodonium (NOX inhibitor), Plumbagin (NOX4 inhibitor ), Apocynine (NOX2 inhibitor), curcumin , EGCG , lovastatin on OECM-1and CA9-22 significantly inhibits production of active form TGF-β1 induce by phenytoin. These results suggested that the increased activated TGF-β levels is regulated by ROS and ROS came from NOX2 and NOX4. Furthermore, curcumin significantly inhibited phenytoin increased TGF-β1 activation in OECM-1and CA9-22.Curcumin could be a potential medicine for prevention and therapy of GO. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T02:38:07Z (GMT). No. of bitstreams: 1 ntu-106-R03450018-1.pdf: 1470337 bytes, checksum: 811d7926ff89fb5f0d9d5298472ba7e3 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 口試委員會審定書………………………………………………………I
謝誌………………………………………………………………………II 中文摘要…………………………………………………………………………III ABSTRACT…………………………………………………………………IV 目錄………………………………………………………………………V 導論 第一節 牙齦過度增生 ( GINGIVAL OVERGROWTH )…………………1 1-1 牙齦過度增生………………………………………………………1 1-2 牙齦過度增生的流行病學…………………………………………3 1-3 牙齦過度增生的致病機制…………………………………………3 1-4 牙齦過度增生的治療………………………………………………4 第二節 二本妥因 (PHENYTOIN)…………………………………………5 2-1 Phenytoin的簡介……………………………………………………5 2-2 Phenytoin的作用機轉………………………………………………5 2-3 Phenytoin與牙齦過度增生…………………………………………5 第三節 轉型生長因子-Β (TGF-Β1)……………………………………6 3-1 TGF-β1的簡介………………………………………………………6 3-2 TGF-β1的訊息傳遞路徑……………………………………………7 3-3 TGF-β1與纖維化……………………………………………………9 第四節 過氧化物 (REACTIVE OXYGEN SPECIES，ROS)………………10 4-1 ROS的簡介…………………………………………………………10 4-2 ROS與纖維化………………………………………………………11 4-2 NADPH oxidase 2與纖維化……………………………………….12 4-3 NADPH oxidase 4與纖維化……………………………………….13 第五節 薑黃素 ( CURCUMIN )…………………………………………14 研究目的…………………………………………………………………15 材料與方法………………………………………………………………16 第一節 細胞株與細胞培養………………………………………………16 第二節 藥物處理…………………………………………………………16 第三節 西方墨點法………………………………………………………18 第四節ENZYME LINKED IMMUNOSORBENT ASSAY (ELISA)………………20 第五節SI-RNA轉染 (TRANSFECTION)….…………………………………21 第六節 統計與方法………………………………………………………21 結果…………………………………………………………………………22 Phenytoin誘導表皮-間質 轉換…………………………………………22 Phenytoin 誘導牙齦表皮細胞株產生p-Smad3…………………………22 TGF-β、ALK5抑制劑會抑制Phenytoin產生的p-Smad3表現……………22 Phenytoin誘導牙齦表皮細胞株釋放活化態TGF-β……………………23 Phenytoin經由NOX2、NOX4誘導牙齦表皮細胞株釋放活化態TGF-β…23 Curcumin、EGCG、Lovastatin 可抑制Phenytoin 釋放活化態TGF-β…24 Curcumin可抑制Phenytoin 釋放活化態TGF-β…………………………24 討論…………………………………………………………………………25 圖與表………………………………………………………………………26 參考文獻…………………………………………………………………34 | |
| dc.language.iso | zh-TW | |
| dc.subject | 上皮-間質細胞轉換 | zh_TW |
| dc.subject | 活性氧化物 | zh_TW |
| dc.subject | 潛在的轉化生長因子 | zh_TW |
| dc.subject | 牙齦過度增生 | zh_TW |
| dc.subject | 苯妥因 | zh_TW |
| dc.subject | EMT | en |
| dc.subject | Phenytoin | en |
| dc.subject | Gingival overgrowth | en |
| dc.subject | Latent TGF-β | en |
| dc.subject | ROS | en |
| dc.subject | EMT | en |
| dc.subject | Phenytoin | en |
| dc.subject | Gingival overgrowth | en |
| dc.subject | Latent TGF-β | en |
| dc.subject | ROS | en |
| dc.title | Phenytoin 經由活性氧誘導牙齦上皮細胞活化潛伏性 TGF-β | zh_TW |
| dc.title | Phenytoin activated latent TGF-β through reactive oxygen species in gingival epithelial cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張瑞青(jennyzc@ms3.hinet.net.),周涵怡 | |
| dc.subject.keyword | 苯妥因,牙齦過度增生,潛在的轉化生長因子,活性氧化物,上皮-間質細胞轉換, | zh_TW |
| dc.subject.keyword | Phenytoin,Gingival overgrowth,Latent TGF-β,ROS,EMT, | en |
| dc.relation.page | 41 | |
| dc.identifier.doi | 10.6342/NTU201703520 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| Appears in Collections: | 口腔生物科學研究所 | |
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| File | Size | Format | |
|---|---|---|---|
| ntu-106-1.pdf Restricted Access | 1.44 MB | Adobe PDF |
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