作者：Laurie Barclay, MD
出處：WebMD醫學新聞
October 20, 2008 — 根據發表於10月號Archives of Dermatology期刊的研究結果，光動力療法，包括局部使用的五胺基酮戊酸(5-ALA)或者其他光活化藥物與曝露於光源，可以產生分子方面的改變，而改善老化皮膚的外觀。
密西根大學醫學院的Jeffrey S. Orringer醫師等人寫道，眾所皆知，皮膚曝露於紫外光下的損害；但是，許多可見光、紅外線雷射與光源，有報告指出可以讓皮膚外觀產生正面的臨床與組織改變；最近幾年，使用光敏感成份來促進一些以光為基礎的治療觀念漸獲支持。
本研究的目標是定量測量光動力治療下，上皮與真皮細胞和分子變化，總共有25名年紀在54至82歲的成人志願者，臨床顯示有前臂皮膚光損害；以局部5-ALA治療3小時之後，脈衝染料雷射設定在不會引起紫斑下進行治療，研究者進行一系列的活體生化與免疫組織化學分析，研究開始時與治療後各時間點的切片樣本。
標記研究包括上皮增殖(Ki67)、上皮損傷(細胞角質蛋白16)與光損害(p53)，以及各種真皮膠原產生的標記，例如prolyl 4-hydroxylase、熱休克蛋白47，與第1型前膠原蛋白；以即時反轉錄酶-聚合酶連鎖反應技術量化第1型和第3型膠原，以酵素連結免疫吸附法量化第1型前膠原蛋白。
光動力治療與刺激上皮增殖有關，證據是增加5倍的Ki67 (P < .05)、上皮厚度增加1.4倍以上(P < .05)；細胞角質蛋白16增加為開始時的將近70倍(P < .05)，表示上皮傷害。膠原往上調節的證據包括增加了第1型前膠原蛋白訊息RNA (2.65倍; P < .05)、第3型前膠原蛋白訊息RNA (3.32倍; P < .05)、第1型前膠原蛋白(2.42倍; P < .05)。
在急性時間點，開始時的上皮p53值與細胞角質蛋白16值有關，也與尖峰膠原產生有關。
作者寫道，特定治療處方的光動力治療產生統計上顯著量化的皮膚分子變化(例如產生第1型和第3型膠原)，和改善皮膚外觀有關。開始時的上皮53免疫染色值可以用來預測對此治療的真皮反應。比較單用脈衝染料雷射者的組織資料，顯示使用光敏感劑可以促進真皮重組。
本研究的限制包括缺乏其他治療參數之一般性、也未提及運用到臉部皮膚的可能性，此研究並未設計直接比較脈衝染料雷射/光動力治療效果與單用脈衝染料雷射者，且此研究非隨機設計。
研究作者結論表示，雖然我們的分子測量還未精準預測單一病患的臨床結果，但整合之後則與大部份臨床文獻相當，因此可以支持此一領域其他研究者發表的臨床研究結論。
研究作者指出，我們相信，特定治療介入引起的真皮修補與再生數量很可能是產生臨床回春的基礎，因此，我們希望有一天，藉由後續發展，我們研究的分子模式具有可以用來預測皮膚美容醫學新技術的臨床價值。
密西根大學皮膚科的The Human Appearance Research Program (HARP)支持此研究。作者宣稱沒有相關資金上的往來。
Photodynamic Therapy May Improve Appearance of Aging Skin
By Laurie Barclay, MD
Medscape Medical News
October 20, 2008 — Photodynamic therapy, which involves topical use of 5-aminolevulinic acid (5-ALA) or other light-activated medication and exposure to a light source, appears to produce changes at the molecular level to improve the appearance of aging skin, according to the results of a study reported in the October issue of Archives of Dermatology.
"The deleterious effects of exposure of the skin to [ultraviolet] irradiation are well established," write Jeffrey S. Orringer, MD, from the University of Michigan Medical School, Ann Arbor, and colleagues. "Alternatively, several visible and infrared lasers and light sources have been reported to produce various positive changes in the clinical and histologic appearance of the skin. In recent years, the concept of employing a photosensitizing compound to enhance the effects of some light-based therapies has been espoused."
The goal of this study was to measure quantitatively the epidermal and dermal cellular and molecular changes associated with photodynamic therapy in a volunteer sample of 25 adults, aged 54 to 83 years, with clinically evident photodamage of the forearm skin. After treatment with topical 5-ALA for 3 hours and pulsed-dye laser treatment using settings that would not induce purpura, the investigators performed serial in vivo biochemical and immunohistochemical analyses on biopsy specimens obtained at baseline and at various times after treatment.
Markers studied included those of epidermal proliferation (Ki67), epidermal injury (cytokeratin 16), and photodamage (p53), as well as various markers of dermal collagen production, such as prolyl 4-hydroxylase, heat shock protein 47, and type 1 procollagen. Type 1 and type 3 collagens were quantified with real-time reverse transcriptase–polymerase chain reaction technology, and type 1 procollagen protein was quantified with enzyme-linked immunosorbent assay.
Photodynamic therapy was associated with stimulated epidermal proliferation, as evidenced by a greater than 5-fold increase in Ki67 (P < .05) and a greater than 1.4-fold increase in epidermal thickness (P < .05). Cytokeratin 16 levels were increased to nearly 70-fold of baseline levels (P < .05), suggesting epidermal injury. Evidence of collagen upregulation included increased procollagen 1 messenger RNA (2.65-fold; P < .05), procollagen 3 messenger RNA (3.32-fold; P < .05), and procollagen 1 protein (2.42-fold; P < .05).
At acute time points, the baseline epidermal p53 level correlated with cytokeratin 16 levels, which were also correlated with peak collagen production.
"Photodynamic therapy with the specific treatment regimen employed produces statistically significant quantitative cutaneous molecular changes (e.g., production of types I and III collagen) that are associated with improved appearance of the skin," the study authors write. "Baseline epidermal p53 immunostaining levels may be predictive of dermal responses to this therapy. Comparison with historical data using pulsed-dye laser therapy alone suggests that use of the photosensitizer may enhance dermal remodeling."
Limitations of this study include lack of generalizability to other treatment parameters and possibly to facial skin, that the study was not designed to directly compare the pulsed-dye laser/photodynamic therapy effect with that of the pulsed-dye laser alone, and the study's nonrandomized design.
"Although our molecular measurements cannot yet precisely predict clinical outcomes for a single given patient, taken together they are very much in keeping with the bulk of the clinical literature and thus lend substantial support to the conclusions reached by other researchers who have published purely clinically oriented work in this field," the study authors conclude.
"We believe that the quantitative amount of dermal repair and regeneration induced by a specific therapeutic intervention very likely underlies the degree of clinical rejuvenation produced. Thus, it is our hope that, with further development, our working molecular model may one day be used to predict the clinical value of new technologies in aesthetic dermatology," the study authors add.
The Human Appearance Research Program (HARP) of the Department of Dermatology, University of Michigan, supported this study. The authors have disclosed no relevant financial relationships.
Arch Dermatol. 2008;144(10):1296–1302.
[ 本帖最後由 goodcat1111 於 2008-10-30 09:23 編輯 ] |
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