Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University, Harbin 150081, PR China.
J Photochem Photobiol B. 2010 Oct 5;101(1):9-15. doi: 10.1016/j.jphotobiol.2010.06.005. Epub 2010 Jul 1.
Photodynamic therapy (PDT) has been shown to attenuate atherosclerotic plaque progression and decrease macrophage-infiltration. The effectiveness of PDT depends strongly on the type of photosensitizers. Hematoporphyrin monomethyl ether (HMME) is a promising second-generation porphyrin-related photosensitizer for PDT. This study is designed to characterize effects of HMME-based PDT on THP-1 cell-derived macrophages and define the cell-death pathway. HMME was identified to accumulate in the macrophages by fluorescence microscopy and confocal scanning laser microscope. Our data demonstrated that the intensity of laser-induced HMME fluorescence in macrophages steadily increased with the increasing incubation concentration of HMME. The survival rate of macrophages determined by MTT assay decreased with the increasing HMME concentration and irradiation time. HMME-based PDT induced macrophage apoptosis via caspase-9 and caspase-3 activation pathway detected by caspase fluorescent assay kit and flow cytometer. The PDT increased the number of apoptotic macrophages by 14-fold at 12 h post irradiation by 9 J/cm(2) 635 nm diode laser. These results imply that photodynamic therapy with HMME may therefore be a useful clinical treatment for unstable atherosclerotic plaques.
光动力疗法（PDT）已被证明可以抑制动脉粥样硬化斑块的进展并减少巨噬细胞浸润。PDT 的效果强烈依赖于光敏剂的类型。血卟啉单甲醚（HMME）是一种很有前途的第二代卟啉类光敏剂，可用于 PDT。本研究旨在描述基于 HMME 的 PDT 对 THP-1 细胞源性巨噬细胞的作用，并确定细胞死亡途径。荧光显微镜和共聚焦扫描激光显微镜显示 HMME 在巨噬细胞中积累。我们的数据表明，巨噬细胞中激光诱导的 HMME 荧光强度随 HMME 孵育浓度的增加而稳定增加。MTT 测定法确定的巨噬细胞存活率随 HMME 浓度和辐照时间的增加而降低。通过 caspase 荧光测定试剂盒和流式细胞仪检测到 caspase-9 和 caspase-3 激活途径，证实基于 HMME 的 PDT 诱导巨噬细胞凋亡。9 J/cm(2)635nm 二极管激光照射 12 小时后，PDT 将凋亡的巨噬细胞数量增加了 14 倍。这些结果表明，HMME 的光动力疗法可能是不稳定动脉粥样硬化斑块的一种有用的临床治疗方法。
