抗坏血酸对血卟啉衍生物渗入肿瘤组织及其光敏作用的影响

Effect of ascorbate on the permeation and photosensitizing activity of hematoporphyrin derivative (HPD) in tumor

目的了解肿瘤组织在血卟啉衍生物及抗坏血酸溶液中浸泡一定时间后，血卟啉衍生物渗入瘤组织的深度、在瘤组织中的含量及抗坏血酸对其渗入和光敏作用的影响。方法以小鼠Ｓ１８０实体瘤和光敏剂癌光啉（ＰｓＤ－００７）为材料，将肿瘤组织分别浸泡在ＰｓＤ－００７（浸Ⅰ组）及ＰｓＤ－００７－抗坏血酸（浸Ⅱ组）溶液中１小时，并以静脉注入ＰｓＤ－００７２４小时的肿瘤为对照（静注组）。通过紫外光照射，观察肿瘤组织中ＰｓＤ－００７红色荧光，测定肿瘤组织中ＰｓＤ－００７和丙二醛含量。结果（１）肿瘤横剖面及肿瘤组织冰冻切片在紫外光照射下所显示的ＰｓＤ－００７红色荧光，浸Ⅰ组和浸Ⅱ组均强，且外周强于中心部位；而静注组则弱，但分布均匀。（２）肿瘤中心部组织匀浆中，ＰｓＤ－００７和丙二醛含量均为浸Ⅱ组＞浸Ⅰ组＞静注组（Ｐ＜０．０５）。结论ＰｓＤ－００７及抗坏血酸均能通过浸泡渗入肿瘤组织，抗坏血酸有促进ＰｓＤ－００７渗入肿瘤组织和增强ＰｓＤ－００７光敏反应的作用。

Objective To determine the depth of permeation and concentration of HPD in tumor tissue which had been immersed in HPD in the presence and absence of ascorbic acid, and to examine its photosensitizing effect. Methods Solid S 180 sarcoma of 1 cm 3 in size was excised from tumor bearing mice and immersed in HPD (PsD 007) 1mg/ml normal saline (group Ⅰ), or HPD (PsD 007) 1 mg/ml plus ascorbic acid 20 mg/ml normal saline (group Ⅱ) for 1 hr. For comparison, HPD (PsD 007) 10mg/kg was injected intravenously to mice bearing tumor of similar size and the tumor was excised 24 hr later(group Ⅲ). Results When the tumors were cross sectioned and UV (370 nm) irradiated, red fluorescence was mainly at the periphery of tumors that had been immersed in HPD whereas the fluorescence was weaker and more evenly distributed in tumors of mice that had received HPD iv. Similar features were observed under fluorescence microscope in frozen sections of identically treated tumors. The concentration of PsD 007 (μg/g) and malondialdehyde (nmol/L) in the tumor homogenates was higher in tumors that had been immersed in PsD 007 plus ascorbate than in tumors immersed in PsD 007 alone. Tumors of mice that had received PsD 007 iv had the lowest concentration of both PsD 007 and malondialdehyde. Conclusion Ascorbate facilitates permeation of HPD into tumor and enhances the photo dynamic effect of HPD