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联合激光与局部雷帕霉素抗血管生成疗法进行长期血管清除:对鲜红斑痣有效治疗的意义

Long-term blood vessel removal with combined laser and topical rapamycin antiangiogenic therapy: implications for effective port wine stain treatment.

作者信息

Jia Wangcun, Sun Victor, Tran Nadia, Choi Bernard, Liu Shaiw-wen, Mihm Martin C, Phung Thuy L, Nelson J Stuart

机构信息

Beckman Laser Institute, University of California, Irvine, California 92617-3010, USA.

出版信息

Lasers Surg Med. 2010 Feb;42(2):105-12. doi: 10.1002/lsm.20890.

Abstract

BACKGROUND AND OBJECTIVES

Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin's normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to (1) investigate whether topical RPM can inhibit reperfusion of photocoagulated blood vessels in an animal model and (2) determine the effective RPM concentration required to achieve this objective.

STUDY DESIGN/MATERIALS AND METHODS: For both laser-only and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian hamsters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure.

RESULTS

In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5-14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group. We also found that the reperfusion rate was not linearly proportional to the RPM concentration.

CONCLUSIONS

With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks.

摘要

背景与目的

对于大多数患者而言,激光治疗后葡萄酒色斑(PWS)胎记完全消退的情况极为罕见。我们推测,治疗效果不佳或治疗失败是由于与皮肤正常伤口愈合反应相关的血管生成导致光凝血管再生和再血管化所致。雷帕霉素(RPM)是一种抗血管生成药物,已被证明可抑制病理性血管的生长。我们的目的是:(1)在动物模型中研究局部应用RPM是否能抑制光凝血管的再灌注;(2)确定实现这一目标所需的有效RPM浓度。

研究设计/材料与方法:对于仅接受激光治疗和接受激光联合RPM治疗的动物,用激光脉冲对植入金黄地鼠背部的视窗腔内的血管进行光凝。用彩色数码摄影和激光散斑成像记录血管的结构和血流动力学,以评估光凝和再灌注情况。对于联合治疗组,在激光照射后每天在视窗的表皮侧局部应用RPM,持续14天。

结果

在仅接受激光治疗的组中,24条光凝血管中有23条在5 - 14天内实现再灌注。在使用不同RPM配方和浓度的联合治疗组中,36%的总体再灌注率远低于仅接受激光治疗的组。我们还发现再灌注率与RPM浓度并非呈线性比例关系。

结论

局部应用RPM可显著降低血管再灌注频率,这意味着光疗与局部抗血管生成联合治疗可能是提高PWS胎记治疗效果的一种有前景的方法。

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