新型光敏剂ZnPcS_4-BSA对荷瘤裸鼠的体内光动力杀伤效应及其机制

InVivoPhotodynamic Killing Effect of the New Photosensitizer ZnPcS_4-BSA in Nude Mice and Its Mechanism

目的探讨新型光敏剂四磺酸酞菁锌与牛血清白蛋白的配合物(ZnPcS4-BSA)介导的光动力疗法(PDT)对胶质瘤的体内光动力杀伤效应,并分析其杀伤机制。方法建立裸鼠胶质瘤模型,将30只荷瘤裸鼠随机分为5组:荷瘤对照组、单纯光照组、单纯光敏剂组、低剂量PDT组和高剂量PDT组,经不同处理后处死裸鼠,切除肿瘤,比较各组抑瘤率、血管内皮生长因子(VEGF)表达水平、微血管密度(MVD)以及凋亡指数。结果抑瘤率、VEGF水平、MVD、凋亡指数等指标检测显示,荷瘤对照组、单纯光照组、单纯光敏剂组3组间差异均无统计学意义,而高、低剂量PDT组均显著高于其它各组,且高剂量PDT组高于低剂量PDT组。结论 ZnPcS4-BSA对荷U251胶质瘤的裸鼠具有良好的光动力效能,其介导的PDT过程存在诱导肿瘤细胞凋亡这一机制,在肿瘤组织中VEGF表达在PDT后升高。

Objective To examine the in-vivo photodynamic killing effect of the novel photosensitizer ZnPcS4-BSA on glio- ma tumors and explore its mechanism. Methods A total of 30 glioma bearing nude mice were divided into 5 groups at random： glioma-bearing group, irradiation group, photosensitizer group, low-dose photodynamic therapy （PDT） group and high-dose PDT group. After receiving different treatments, the mice in each group were sacrificed for removal of the xenograft tumors. The tumor inhibition rate, the vascular endothelial growth factor （VEGF） expression, the microvessel density （MVD） and the apop- totic index were compared among groups. Results There was no significant difference in the tumor inhibition rate, the VEGF expression,the MVD and the apoptotic index among the glioma-bearing group, the irradiation group and the photosensitizer group. However,these indices were significantly higher in the low-dose and high dose PDT groups,with the effect of high dose PDT superior to that of low-dose PDT. Conclusion The novel photosensitizer ZnPcS4-BSA has a good photodynamic killing effect in glioma-bearing nude mice. The mechanism involves the inducement of apoptosis during the PDT and the increased expression of VEGF after PDT.