Rosin Flávia Cristina Perillo, Barcessat Ana Rita Ribeiro, Borges Giuliana Gadoni Giovanni, Ferreira Luciana Gonçalves Valente, Corrêa Luciana
General Pathology Department, School of Dentistry, University of São Paulo, Av. Prof Lineu Prestes, 2227 - Cidade Universitária, 05508-000, São Paulo, SP, Brazil.
Health Department, School of Nursing, Federal University of Amapá, Rod. Juscelino Kubitschek, KM-02 Jardim Marco Zero Macapá, 68.903-419, Macapá, AP, Brazil.
Lasers Med Sci. 2017 Feb;32(2):379-387. doi: 10.1007/s10103-016-2127-0. Epub 2016 Dec 21.
Impairment of vascular functions after photodynamic therapy (PDT) is frequently associated with tumor remission and is considered one of the main antineoplastic PDT effects. Vascular alterations in oral leukoplakia (OL) treated with PDT have not yet been described. The aim of this study was to evaluate the effect of topical 5-ALA-mediated PDT on the vascular network of 4NQO-induced OL in rats. After applying 4NQO topically on the tongue during 16 weeks, there was induction of dysplastic lesions, which were treated with two PDT sessions (with an interval of 72 h between them), using topical application of 5-ALA and posterior irradiation with a laser (90 J/cm fluency). Histological sections of the tongues were obtained and analyzed concerning plasmatic exudation and microvessel density after immunolabeling with CD31 and CD34 vessel markers. There was intense plasmatic exudation after 6 h of the first PDT session; at 6 h of the second PDT session, there was a significant reduction in the density of CD31- and CD34-positive microvessels in comparison to controls (p < 0.05). In the PDT intervals, there was an increase in the density of CD31 and CD34 microvessels, suggesting angiogenesis. Topical application of 5-ALA-mediated PDT caused an immediate deleterious effect on the vascular network, increasing vessel permeability and reducing vessel density, mainly after two sessions of the treatment. However, secondary angiogenesis emerged in these lesions during intervals of the PDT session. This fact may be considered during the adoption of a PDT protocol, to avoid OL resistance and recurrence after the treatment.
光动力疗法（PDT）后血管功能受损常与肿瘤缓解相关，被认为是PDT主要的抗肿瘤作用之一。PDT治疗口腔白斑（OL）后的血管改变尚未见报道。本研究旨在评估局部5-氨基酮戊酸介导的PDT对4-硝基喹啉-1-氧化物诱导的大鼠OL血管网络的影响。在16周内局部将4-硝基喹啉-1-氧化物涂于大鼠舌部后，诱导出发育异常病变，采用两次PDT治疗（两次治疗间隔72小时），局部应用5-氨基酮戊酸并随后用激光照射（能量密度90 J/cm²）。获取舌部组织切片，在用血管标志物CD31和CD34进行免疫标记后，分析血浆渗出和微血管密度。第一次PDT治疗6小时后出现强烈的血浆渗出；第二次PDT治疗6小时时，与对照组相比，CD31和CD34阳性微血管密度显著降低（p < 0.05）。在PDT治疗间隔期，CD31和CD34微血管密度增加，提示血管生成。局部应用5-氨基酮戊酸介导的PDT对血管网络产生即时有害影响，增加血管通透性并降低血管密度，主要在两次治疗后出现。然而，在PDT治疗间隔期这些病变中出现了继发性血管生成。在采用PDT方案时可能需要考虑这一事实，以避免OL治疗后产生耐药性和复发。
