【作者】 郑江华；

【导师】 时德；

【作者基本信息】 重庆医科大学 ， 外科学， 2006， 博士

【摘要】 光动力疗法(photodynamic therapy,PDT)是指光敏剂选择性地聚集在肿瘤组织中,接受光照后在细胞内产生活性氧物质,而导致肿瘤细胞凋亡或坏死的一种治疗方法。迄今为止,加拿大、美国、法国、荷兰、德国和日本等国家已先后批准PDT用于一些恶性肿瘤,但常规光敏剂副反应重和需要较长时间避光等缺点又限制了其进一步临床应用。δ氨基酮戊酸(aminolevulinic acid,ALA)-PDT是基于ALA孵育癌细胞后产生内源性原卟啉Ⅸ(protoporphyrin,PPIX),并绕过血红素的反馈调节机制,最终导致血红素前体物质-PPIX(光敏剂)在癌细胞内积累,用可见光照射后将导致癌细胞的破坏。因ALA副作用小,所以ALA-PDT是一种很有前途的治疗方法。在结肠癌体外和体内实验研究表明,ALA诱导的PPIX均高于常组织,PDT后可明显杀伤癌细胞,但杀伤作用还不够强,为进一步增强PDT对结肠癌细胞的作用效果,探讨其作用的信号传导机制是重要的研究方向之一。ALA-PDT能诱导很多细胞系发生细胞凋亡,但其所诱导的细胞凋亡是否存在钙信号途径仍不清楚。有丝分裂原蛋白激酶(mitogen activated protein kinases, MAPKs)信号通路在肿瘤的放疗和化疗中起着重要作用,但在ALA-PDT对结肠癌细胞中的作用也不清楚。更多还原

【Abstract】 Photodynamic therapy(PDT) of cancer is based on the tumor-specific accumulation of a photosensitizer, followed by irradiation with visible light, reactive oxygen species(ROS) is generated, which induces cell death and apoptosis. So far, PDT of some malignant tumors has been ratified by Canada, American, French, Dutch Germany, Japan and so on. But common photosensitizer needs patients to avoid light exposure for more than 20 days and it have many side effects, whose drawbacks may limit applicability of PDT in treatment of tumors.δ-aminolevulinic acid(ALA)-PDT based on endogenously formed protoporphyrin IX (PPIX) following incubation of cells withδ-aminolaevulinic acid. By this procedure the feedback control of haem biosynthesis is bypassed and high amounts of ultimate heme precursor, the photosensitizing compound PPIX, are accumulated in cancerous cells. Subsequent irradiation of ALA-treated cells with visible light leads to destruction of cancerous cell. ALA-PDT is a更多还原