【摘要】 5 氨乙酰丙酸 (ALA)可在肿瘤内诱导原卟啉区 (PpIX)光敏剂形成 ,但其亲脂性极差 ,进入细胞的能力有限。脂化的ALA衍生物能增强其进入细胞的能力 ,增进细胞中PpIX的合成。比较了氨乙酰丙酸己酯 (He ALA)与ALA对肝癌细胞中PpIX的生成及光动力损伤作用。细胞的荧光显微图象显示 ,经He ALA培育后 ,细胞中生成了PpIX。PpIX分布在细胞质中 ;细胞的荧光光谱显示出PpIX的特征荧光峰 ,证实细胞中PpIX的生成。实验发现 ,0 .2mmol/L的He ALA药物浓度与 2mmol/LALA的药物浓度在细胞中生成的PpIX含量相当 ;予以相同剂量的光照射后 ,两者对细胞的光敏损伤程度相近 ,反映He ALA对癌细胞有更高的光动力损伤功效。因此在光动力治疗的应用中 ,He ALA是一种极有开发前景的新药物更多还原

【Abstract】 Aminolevulinic acid (ALA) is a precursor to heme synthesis pathway and currently used to induce endogenous protoporphyrin IX (PpIX, a potent photosensitizer) for photodynamic therapy of cancer. ALA has, however, a limited ability to cross cellular membranes due to its low lipid solubility. The use of lipophilic ALA esters may increase cellular uptake, that results in an enhanced PpIX synthesis. In the present study, a comparison of ALA and its hexyl ester (He ALA) was made in the QGY human hepatoma cell line with respect to PpIX production and its photocytotoxicity. The fluorescence emission spectrum of the cells incubated with He ALA was identical to that of PpIX, indicating that He ALA could induce PpIX in the cells. Fluorescence images demonstrated that the He ALA induced PpIX was localized in the cytoplasm of the cells. Moreover, a similar amount of PpIX was found in the cells incubated with 0.2 mmol/L He ALA or 2 mmol/L ALA and a similar level of cell survival was reached following light exposure. These results suggest that He ALA is much more efficient at producing PpIX and photocytotoxicity than ALA itself in the cells.更多还原