陳冬生Chen, Tung-Sheng林冠宇Lin, Kuan-Yu2022-06-089999-12-312022-06-082020https://etds.lib.ntnu.edu.tw/thesis/detail/517a07d4687b93b1ad0c409cea04b27b/http://rportal.lib.ntnu.edu.tw/handle/20.500.12235/118619['紫外燈（UV）可以誘導皮膚組織的光老化，但從幹細胞釋放的生長因子顯示出，對紫外燈誘導的皮膚老化具有抗老化作用。杜鵑花酸對細胞有保護的作用，但作用機制仍然不清楚。這項研究調查了用杜鵑花酸處理前後的間葉幹細胞，對於治療紫外燈誘導的皮膚老化，是否能表現出不一樣的抗老化作用。體外研究證實，杜鵑花酸可透過增加幹細胞膜蛋白CXCR4的表現來促進旁分泌。另外本研究發現老化標記miRNA-7850-5p在老化的皮膚細胞中其表現量被往下調降。接下來，將UV誘導老化的皮膚細胞放入幹細胞條件培養基中，研究發現，與一般幹細胞相比，經杜鵑花酸處理強化過的幹細胞條件培養基對miRNA-7850-5p有更好的提升作用。這表示用杜鵑花酸預處理的幹細胞條件培養基可通過調節衰老標記miRNA-7850-5p來抑制UV誘導皮膚細胞中的老化信號。動物研究證實，在紫外燈加幹細胞條件培養基治療組和紫外燈加杜鵑花酸強化幹細胞條件培養基治療組，其表皮和膠原蛋白的厚度均有改善的效果，而且皮下毛囊的數目均有增加的趨勢。另外在老化的標記蛋白p53和p21的表現量均有下降的趨勢，而膠原蛋白的標記蛋白Collagen 1 A1的表現量均有上升的趨勢。但在經過觀察後，紫外燈加杜鵑花酸強化幹細胞條件培養基治療組中的表皮、膠原蛋白、皮下毛囊、老化的標記蛋白p53和p21、膠原蛋白的標記蛋白Collagen 1 A1相較於紫外燈加幹細胞條件培養基治療組有更好的改善效果。結論，幹細胞條件培養基在改善皮膚老化有明顯的治療潛力，而在使用杜鵑花酸強化幹細胞條件培養基有更明顯的治療效果。']['Ultraviolet rays (UV) can induce photoaging of skin tissues, and growth factors released from stem cells have shown anti-aging effects on UV-induced skin aging. Azelaic acid has a protective effect on cells, but the mechanism is still unclear. This study investigated whether the mesenchymal stem cells with or without Azelaic acid pre-incubation can show different anti-aging effects for the treatment of UV induced skin aging. In vitro studies have confirmed that azelaic acid can promote paracrine through increasing the expression of stem cell membrane protein CXCR4. In contrast, I found that the aging marker miRNA-7850-5p is down-regulated in aging skin cells. Next, I put the aging skin cells into stem cell conditioned medium. Compared to stem cells, I found that stem cell conditioned medium pre-treated with azelaic acid has a better effect on expression of miRNA-7850-5p. This result indicates that the stem cell conditioned medium pretreated with azelaic acid can inhibit UV-induced aging signals in skin cells by adjusting the senescence marker miRNA-7850-5p. In animal study compared to stem cell conditioned medium without azelaic acid pre-treatment, the thickness of epidermis, collagen production and the number of subcutaneous hair follicles were improved in stem cell conditioned medium with azelaic acid pre-treatment. In addition, both of the aging marker p53 and p21 have downregulated and collagen 1 A1 was expressed in stem cell conditioned medium with azelaic acid pretreatment. Furthermore the epidermis, collagen production, number of subcutaneous hair follicles, aging marker proteins p53 and p21, and expression of Collagen 1 A1, were improved in the stem cell conditioned medium with azelaic acid pre-treatment than conditioned medium without azelaic acid pre-treatment. In conclusion, stem cell conditioned medium with azelaic acid pre-treatment has better therapeutic potential in improving skin aging than stem cell conditioned medium without azelaic acid pre-teatment.']杜鵑花酸幹細胞皮膚老化微小分子核糖核酸Azelaic acidStem cellsSkin AgingMicroRNA學術論文