臺灣博碩士論文加值系統

世界上有眾多的患者罹患慢性皮膚傷口，這些傷口往往合併抗藥性細菌感染，針對這些難以癒合的皮膚傷口，試著去研發其他有效的治療方法是一個極其重要的臨床課題。本研究中，我們成功地以光動力療法治療三位罹患慢性感染傷口的病患，這些傷口在接受光動力療法後逐漸癒合，原本具有感染的傷口在進行光動力療法後再也沒有分離出細菌，在生體外實驗中我們亦發現光動力療法可有效抑制細菌增生。在細胞移行實驗中，我們發現光動力療法可能藉由刺激皮膚角質細胞分泌介白素6進而促進細胞移行，我們並進一步以糖尿病小鼠皮膚傷口模式中，探討光動力療法可以促進傷口癒合的可能機轉。綜合以上初步的研究結果，光動力療法可能未來應用在慢性感染傷口治療上極具發展潛力。

Non-healing skin ulcers affect billions of people around the world. Antibiotics-resistant bacteria are often isolated from these chronic ulcers. It is imperative to search for alternative, effective treatments for such non-healing skin ulcers. In this study, we reported successful photodynamic therapy to enhance healing of chronic infected ulcers of three patients who were refractory to multiple conventional treatments. These ulcers healed after low-dose photodynamic therapy and there was no recurrence up to 30 months post-treatment. Interestingly, no bacteria were isolated from the ulcers after PDT treatment. Photoinactivation of bacterial growth is also evident in vitro. Furthermore, In vitro wounding assay showed that PDT-enhanced migration of keratinocytes may be mediated by IL-6. Finally, we tried to explore the underlying mechanism in PDT-treated full-thickness skin wound of diabetic mice. These results suggest that PDT may be an effective, alternative treatment for patients with recalcitrant infected ulcers.

English abstract 2
Chinese abstract 3
Acknowledgement 4
Figures/Tables contents 7
Abbreviations 8

Chapter 1. Introduction 9
1.1 Background 10
Photodynamic therapy 10
Photosensitizing agents 10
Light sources 11
Photodynamic therapy in dermatology 11
Chronic skin ulcer 13
1.2 Hypothesis and aims 16

Chapter 2. Material and Methods 19
PDT protocols on patients 20
In vitro assay of antibacterial effects of PDT 21
In vitro assay of PDT-induced IL-6 production 21
In vitro wounding assay 22
Animals 22
Full-thickness tail wounding model 23
Statistical analysis 23

Chapter 3. Results 25
Recalcitrant infected leg ulcers successful treated by PDT 26
PDT inhibits bacteria growth in vitro 27
The PDT-enhanced keratinocytes migration is mediated by IL-6 28
PDT accelerates wound healing in diabetic mice 29

Chapter 4. Discussion 42

Chapter 5. Conclusion 48

References 50

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