海姆泊芬光动力通过KLF2-VEGF通路抑制血管再生治疗鲜红斑痣的作用及机制研究

Abnormal capillary dilatation is the main feature of port wine stains and excessive expression of VEGF is the key molecular mechanism. HMME-PDT is clinically effective in the treatment of port wine stains. HMME-PDT has a good effect and a low recurrence rate compared with traditional pulsed dye laser treatment, but the exact mechanism is still unclear. Our study found that abnormally expanded blood vessels and VEGF expression was significantly reduced after treatment. The expression of KLF2 , a key transcription factor of vascular endothelial cells, was also decreased, suggesting that HMME-PDT may inhibit KLF2 and reduce VEGF expression, inhibition of blood vessels Regeneration. Based on previous studies, our project team want to explore the mechanism of HMME-PDT inhibiting the effects of vascular regeneration by decreasing the expression of KLF2 and VEGF through clinical samples, chicken model and human vascular endothelial cells from the in vivo, cellular and molecular levels,and to provide a new theoretical basis to further improve the clinical efficacy and reduce the recurrence rate.

毛细血管异常扩张是鲜红斑痣的主要特征，VEGF高表达是其关键分子机制。海姆泊芬光动力（HMME-PDT）可有效治疗鲜红斑痣，相对于传统方法脉冲染料激光治疗，效果好，复发率低，但其具体机制尚不明确。本课题组研究发现HMME-PDT治疗鲜红斑痣后，异常扩张的血管和VEGF表达明显减少；血管内皮细胞的关键转录因子KLF2表达亦降低，提示HMME-PDT可能抑制KLF2而降低VEGF表达、抑制血管再生。本项目组拟在前期研究基础上，应用临床样本、鸡冠模型和人血管内皮细胞从体内、细胞和分子水平探索HMME-PDT通过降低KLF2和VEGF表达，抑制血管再生作用的机制，为进一步提高临床疗效、降低复发率提供新的理论基础。

背景：临床海姆泊芬光动力（HMME-PDT）治疗鲜红斑痣（PWS）缺乏无创、高效、准确的疗效评价方法且其治疗机制仍不明确，在其治疗过程中，与血管生成相关的因子如Kruppel样因子2（KLF2）、血管内皮生长因子（VEGF）是否下调并发挥抑制血管生成作用，如何发挥作用等科学问题亟待研究。.目的：通过临床样本探索无创诊断技术在HMME-PDT治疗PWS疗效评估中的应用；通过鸡冠及人脐静脉血管内皮细胞（HUVECs）模型探索HMME-PDT治疗PWS的机制。.方法：临床HMME-PDT治疗PWS治疗前后采用无创诊断技术（VISIA-CRTM皮肤分析系统、皮肤镜、高频超声和激光散斑对比成像）对皮损及周围正常皮肤进行标准影像学数据采集，统计分析不同影像学表现的疗效差异。以鸡冠和HUVECs分为动物和细胞模型，从动物和细胞水平探索HMME-PDT治疗PWS中KLF2、VEGF的表达变化，并在细胞水平上进一步探索HMME-PDT治疗PWS中MAPK通路的变化。.结果：VISIA-CRTM 皮肤分析系统可分析皮损颜色消退情况，治疗前后红斑指数差值越大疗效越好；皮肤镜可辅助临床分型及反映治疗后血管破坏程度，指导治疗参数及治疗终点的选择，治疗后即刻出现血管破裂征者疗效好，上述这两者对于疗效评价意义较大；高频超声及激光散斑对比成像检测皮损治疗区治疗前后皮肤厚度及血流灌注，如治疗前皮损超声未见明显线状回声者效果好，治疗后激光散斑成像显示血流信号减少或减弱者效果好；HMME-PDT治疗PWS的动物和细胞研究中KLF2、VEGF表达量明显减少，HMME-PDT后的HUVECs内p-ERK1/2和p-JNK的表达降低，而p-p38表达显著上调。.结论：无创诊断技术可辅助疗效评判，HMME-PDT治疗PWS可能通过KLF2-MAPK-VEGF抑制血管内皮细胞迁移、增殖及管腔结构形成，发挥抑制血管生成的作用。