Parekh S G, Trauner K B, Zarins B, Foster T E, Anderson R R
Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Lasers Surg Med. 1999;24(5):375-81. doi: 10.1002/(sici)1096-9101(1999)24:5<375::aid-lsm8>3.0.co;2-b.
Wound healing is an intricate process requiring the orchestration of cells, growth factors, cytokines, and the extracellular matrix. Cytokines, specifically TGF-beta, are believed to be instrumental in sustaining the fibrotic process, which leads to scarring. Photodynamic therapy (PDT) uses potent photosensitizers, which induce a wide range of effects on cells and the extracellular matrix. The influences of PDT on wound healing are not well known.
STUDY DESIGN/MATERIALS AND METHODS: Seven full-thickness incisional wounds were placed on each of 24 hairless Sprague Dawly rats, three wounds on one flank serving as dark controls and four on the contralateral side treated with PDT. Wounds were created two days before, one hour before, or one hour after red light exposure with an argon ion pumped dye laser. Twelve rats were injected with 0.25 mg/kg or 0.5 mg/kg of the PDT drug, BPD-MA, and the other 12 with 5 mg/kg or 10 mg/kg of the PDT drug, CASP, 3 and 24 hours prior to irradiation of light, respectively. At low doses of both photosensitizers, animals were irradiated with 1, 5, 10, and 20 J/cm2. At higher doses of BPD-MA and CASP animals were treated with 10, 20, 50, and 100 J/cm2 of light. Wounds were examined each day for 14 days and noted for edema, erythema, inflammation, necrosis, and quality of scarring. Wounds were also photographed at day 0, 2, 5, 8, and 14 post-irradiation. All animals were sacrificed 14 days after irradiation and the wounds were evaluated by light microscopy.
Grossly, animals treated with 0.25 mg/kg BPD-MA showed no effect with PDT. Animals treated with 0.5 mg/kg BPD, and 5 and 10 mg/kg CASP showed responses that varied with both light and drug dose. Erythema, edema, inflammation, and necrosis attributed to PDT were all observed, but there was no apparent influence of PDT on either the rate or final appearance of wound healing. Histologically, there were no apparent differences between treated and untreated sites, regardless of the drug, dose of light, or time of irradiation.
A single PDT treatment given before or after skin wounds does not apparently alter wound healing even when PDT caused brisk inflammatory reactions. PDT may have effects that were not detected. We conclude that PDT does not greatly influence incisional skin wound healing in the rat model.
伤口愈合是一个复杂的过程，需要细胞、生长因子、细胞因子和细胞外基质协同作用。细胞因子，特别是转化生长因子-β，被认为在维持导致瘢痕形成的纤维化过程中起重要作用。光动力疗法（PDT）使用强效光敏剂，其对细胞和细胞外基质会产生广泛影响。PDT对伤口愈合的影响尚不明确。
研究设计/材料与方法：在24只无毛斯普拉格-道利大鼠身上各制造7个全层切口伤口，一侧腹的3个伤口作为黑暗对照，对侧的4个伤口用PDT治疗。伤口分别在氩离子泵浦染料激光红光照射前2天、1小时或照射后1小时制造。分别在光照前3小时和24小时，给12只大鼠注射0.25mg/kg或0.5mg/kg的PDT药物维替泊芬（BPD-MA），给另外12只大鼠注射5mg/kg或10mg/kg的PDT药物半胱天冬酶抑制剂（CASP）。对于两种光敏剂的低剂量组，动物分别接受1、5、10和20J/cm²的光照。对于较高剂量的BPD-MA和CASP组，动物接受10、20、50和100J/cm²的光照。连续14天每天检查伤口，记录水肿、红斑、炎症、坏死和瘢痕质量。在照射后第0、2、5、8和14天对伤口拍照。照射14天后处死所有动物，伤口进行光学显微镜评估。
大体观察，用0.25mg/kg BPD-MA治疗的动物经PDT处理后无效果。用0.5mg/kg BPD-MA以及5mg/kg和10mg/kg CASP治疗的动物，其反应随光照和药物剂量而变化。观察到了归因于PDT的红斑、水肿、炎症和坏死，但PDT对伤口愈合的速度或最终外观没有明显影响。组织学上，无论药物、光照剂量或照射时间如何，治疗部位与未治疗部位之间均无明显差异。
即使PDT引起明显的炎症反应，在皮肤伤口之前或之后进行单次PDT治疗显然不会改变伤口愈合。PDT可能有未被检测到的影响。我们得出结论，在大鼠模型中，PDT对切口皮肤伤口愈合影响不大。
