ALA-PDT治疗Fischer 344大鼠颅内9L胶质瘤的实验研究

Experimental Study of ALA-PDT in Fischer 344 Rats with Orthotopic 9L Glioma

观察新型光敏剂5-氨基乙酰丙酸(ALA)介导的光动力学疗法(PDT)治疗Fischer 344大鼠9L胶质瘤的效果并探讨其作用机制。20只雄性Fischer 344大鼠颅内种植9L脑胶质瘤细胞后,随机分为对照组、PDT治疗组(40J/cm2组、80J/cm2组和120J/cm2组)。接种9L细胞7天后治疗组接受相应的ALA-PDT治疗。治疗后第7天处死所有动物,通过Hematoxylin-Eosin(H-E)染色法检测颅内肿瘤的生长情况;利用免疫组化法检测肿瘤细胞的增殖活性(Ki67)和TUNEL法测定肿瘤细胞的凋亡。结果表明利用不同能量的ALA-PDT治疗后大鼠的生存状态明显改善,脑胶质瘤的体积减小,其治疗效果在一定范围内随着能量的增大而增强,但80J/cm2和120J/cm2的治疗效果基本相同。通过对肿瘤细胞增殖和凋亡的检测发现,ALA-PDT对细胞的增殖无影响,但可诱导肿瘤细胞的凋亡。ALA-PDT通过诱导肿瘤细胞的凋亡可有效治疗脑胶质瘤。

The study is to observe the effect of photodynamic therapy （PDT） mediated with new photo sensitizer （5- aminolevulinic acid, ALA） in Fischer 334 rats with 9L glioma glioma and explore its mechanisms. Twenty Fischer 334 rats are implanted 9L cells to brain and randomly subjected to no treatment and PDT treatment （40, 80, 120 J/cm^2 ）. Mter 7-day implantation, rats with PDT treatment are injected ALA at the dose of 300 mg/kg and then receive PDT treatment for 3 h, respectively. All animals are sacrificed after 7-day PDT treatment and the tumor size is measured by Hematoxylin-Eosin （H-E） staining. Immunohistochemical staining for Ki67 and TUNEL staining are used to detect the proliferation of tumor cells and apoptosis, respectively. Different doses of ALA-PDT treatment significantly improves the decreased living status induced by glioma, and significantly reduces gliomas size. These effects depend on the dosage of PDT in some range, but between the two high doses （80 J/cm^2 and 120J/cm^2）, the therapeutic effect has no significantly difference. By detection of tumor cell proliferation and apoptosis respectively, ALA-PDT treatment can lead apoptosis of tumor cells but has no effect on cell proliferation. ALA-PDT can suppress the development of glioma by induction of apoptosis of tumor cells.