- 學位論文
探討薑黃素對皮膚傷口癒合之影響及相關機轉
To study the effects of curcumin on wound healing and the underlying mechanisms
摘要
傷口癒合為一種動態平衡的生理狀態及一系列複雜交互作用的自然修復過程，通常此過程可分為三階段且互相重疊的時期，包括發炎反應、組織增生與組織重建期。傷口癒合不良時會增加感染的危險性，嚴重時會導致截肢，並可能危及生命。長期發炎反應是導致傷口癒合不良的原因。薑黃素是植物薑黃的天然無毒成分並且普遍被認為它具有抗發炎活性，也被報導可加速傷口癒合的潛能，有多項研究指出薑黃素具有抗發炎與治療癌症的潛力，但對於能加強皮膚傷口癒合及其相關機制，則尚待釐清。我們在72隻小鼠背上製造兩個傷口，並於第1,3,5,7,9和12天，局部塗抹僅有Pluronic F127凝膠（20％）或加入薑黃素（0.2mg / mL）的凝膠。以總體外觀評估其傷口大小，利用蘇木精和伊紅染色顯微鏡評估，以免疫組織化學染色看腫瘤壞死因-α和α-平滑肌肌動蛋白的表現，以及運用聚合酶鍊式反應擴增mRNA方法看其表現。 我們發現用加入薑黃素的組別治療可使傷口癒合快速，其主要表現為良好的肉芽組織形成，包含豐厚膠原沉積和再生上皮組成。薑黃素在癒合的早期階段增加了腫瘤壞死因-α mRNA和蛋白質的量，接下來其表現量顯著降低。但是，在同一時期其控制組中的表現仍然很高。在薑黃素處理的傷口中，膠原蛋白的量顯著更高。在第7和第12天，由薑黃素處理的小鼠，在免疫組織化學染色下α-平滑肌肌動蛋白的表現保持增加。薑黃素處理通過核因子-κB信號顯著抑制腫瘤壞死因子-α處理過的纖維母細胞中的基質金屬肽酶-9和刺激的α-平滑肌肌動蛋白濃度。因此，外用薑黃素通過調節各種細胞因子的可加速小鼠的傷口癒合。
並列摘要
Loss of the integrity of large portions of the skin as a result of injury or illness may lead to major disability or even death. Wound healing is a dynamic, interactive process involving inflammation, proliferation and maturation-that overlap in time. The prolonged inflammation often results in poor wound healing. Curcumin is a natural and active constituent of turmeric plant without induction of cytotoxicity. Accumulating evidence has indicated that curcumin has the therapeutic potential for the inflammatory diseases such as cancer and aging. Curcumin was reported to be an anti-inflammatory agent that may accelerate wound healing, but its mechanisms are unclear. We created back wounds in 72 mice and treated them with or without topical curcumin (0.2 mg/mL) in Pluronic F127 gel (20%) daily for 1, 3, 5, 7, 9, and 12 days. Healing in wounds was evaluated from gross appearance, microscopically by hematoxylin and eosin staining, by immunohistochemistry for tumor necrosis factor- and - smooth muscle actin, and by polymerase chain reaction amplification of mRNA expression levels. Treatment caused fast wound closure with well-formed granulation tissue dominated by collagen deposition and regenerating epithelium. Curcumin increased the levels of tumor necrosis factor- mRNA and protein in the early phase of healing, which then decreased significantly. However, these levels remained high in controls. Levels of collagen were significantly higher in curcumin-treated wounds. Immunohistochemical staining for -smooth muscle actin was increased in curcumin-treated mice on days 7 and 12. Curcumin treatment significantly suppressed matrix metallopeptidase-9 and stimulated -smooth muscle actin levels in tumor necrosis factor--treated fibroblasts via nuclear factor B signaling. Thus, topical curcumin accelerated wound healing in mice by regulating the levels of various cytokines.