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研究生:林國成
研究生(外文):LIN, KUO-CHEN
論文名稱:在皮膚纖維母細胞中Hydroxyquinoline-based 衍生物會透過抑制紫外光B造成的細胞毒性
論文名稱(外文):New Hydroxyquinoline-based Derivative Protects Dermal Fibroblasts From Ultraviolet B Irradiation Induced Cytotoxicity
指導教授:闕小輝
指導教授(外文):CHUEH,SHEAU-HUEI
口試委員:王正康劉珮珊
口試委員(外文):WANG,JEHENG-KANGLIU,PEI-SHAN
口試日期:2017-05-19
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:41
中文關鍵詞:皮膚纖維母細胞紫外光B氧化壓力
外文關鍵詞:FibroblastUltraviolet BOxidative Stress
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這篇文章研究新合成的金屬離子螯合劑Hydroxyquinoline-based 衍生物(HLH2),保護人類真皮成纖維母細胞避免因紫外線B(UVB)導致細胞毒性和皮膚老化。UVB的照射會增加細胞內活性氧(Reactive oxygen species, ROS)以及減少NF-E2相關因子2(nuclear factor erythroid-2-related factor, Nrf2),隨後ROS會活化粒線體的凋亡路徑。HLH2可以抑制由UVB照射所造成的NQO-1以及HO-1降低,ROS生成和細胞凋亡。UVB照射會活化12-lipooxygenase 和 12-lipooxygenase 的產物12-hydroxyeicosatetraenoic acid (12-HETE),並誘導鈣離子經由TRPV1進入細胞內。HLH2不是鈣離子螯合劑。HLH2會抑制由12-HETE誘導的細胞內鈣離子增加,但並不會抑制由Bradykinin所造成的細胞內鈣離子增加。總之,我們的結果表明UVB照射所誘導鈣離子增加是經由TRPV1,並且導致細胞產生毒性和皮膚老化,而HLH2會抑制TRPV1通道。是抗皮膚老化治療的發展的潛在化合物。
This study examined whether a newly synthesized metal chelator hydroxyquinoline based derivative, (HLH2), protects human dermal fibroblasts from ultraviolet B (UVB) irradiation-induced cytotoxicity and skin aging. UVB irradiation increased reactive oxygen species (ROS) levels, subsequently ROS activated the mitochondrial apoptotic pathway. HLH2 inhibited the decrease of UVB-irradiation-induced NQO-1 and HO-1 expression, ROS generation and apoptosis. UVB irradiation activated 12-lipooxygenase and the product of 12-lipooxygenase 12-hydroxyeicosatetraenoic acid (12-HETE) induced cytosolic Ca2+ increase via TRPV1 channel. HLH2 was not a Ca2+ chelator. 12-HETE-induced cytosolic Ca2+ increase but not bradykinin was inhibited by HLH2. Taken together, our results suggest that TRPV1 is responsible for UVB irradiation induced Ca2+ increase which subsequently causes cytotoxicity and skin aging and HLH2 inhibits TRPV1 channel and is a potential compound for the development of anti-skin aging therapy.
目錄 Ⅰ
圖文目錄 Ⅱ
縮寫表 III
摘要 V
Abstract VI
第一章 緒論 1
第一節、 真皮層纖維母細胞( Human Dermal fibroblasts, HDFs ) 1
第二節、 紫外光(Ultraviolet, UV) 1
第三節、 活性氧(Reactive oxygen species, ROS) 2
第四節、 銅離子螯合劑(Metal Chelation) 2
第五節、 NF-E2相關因子2 (Nuclear factor (erythroid – derived 2)-like2) 3
第二章 實驗材料與方法 4
第一節、 實驗材料 4
第二節、 實驗方法 7
第三章 實驗結果 13
第一節、 Human dermal fibroblasts 細胞存活率觀察 13
第二節、 HLH2會抑制TRPV1造成胞內鈣離子減少 14
第三節、 藥物對於細胞內鈣離子濃度變化以及Nrf2的影響 15
第四章 討論 17
第五章 結論 19
第六章 參考文獻 36

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