HPPH光动力治疗对鼠G422脑胶质瘤缺氧诱导因子(HIF-1α)、血管内皮生长因子(VEGF)表达的影响  

Research on Expression of HIF-1αand VEGF of Mice G422 Glioma in Response to HPPH-Based Photodynamic Therapy

作　　者：王宇[1] 朱菁[2] 张慧国[2] 张美珏[2] 施虹敏[2] 

机构地区：[1]上海交通大学医学院附属仁济医院神经外科,上海200127 [2]上海交通大学医学院附属仁济医院皮肤科,上海200127

出　　处：《应用激光》2012年第3期251-260,共10页Applied Laser

摘　　要：目的:探讨HPPH光动力治疗对鼠G422脑胶质瘤脑部及腋部皮下移植瘤缺氧诱导因子(HIF-1α)、血管内皮生长因子(VEGF)表达的影响并和HpD-PDT做比较。方法:建立鼠G422脑胶质瘤、腋部皮下移植瘤模型,设立空白对照组、单注射HPPH 0.45mg/kg组、单665nm激光照射组、单630nm激光照射组、HPPH-PDT组(0.15、0.3、0.45mg/kg组)、HpD-PDT 5mg/kg组。单注射HPPH组、HPPH-PDT组和HpD-PDT组自尾静脉推注入光敏剂,24h后以波长665nm的半导体激光照射HPPHPDT组和单激光组肿瘤,功率密度200mW/cm^2,每光斑照射17min,能量密度为204J/cm^2;以波长630nm的半导体激光照射HpD-PDT组肿瘤,功率密度200mW/cm^2,每光斑照射20min,能量密度为240J/cm^2。于PDT后9d处死鼠,取肿瘤、肿瘤边缘、正常脑组织及血液,行酶联免疫吸附法(ELISA)的双抗体夹心法检测HPPH-PDT和HpD-PDT后及对照组缺氧诱导因子(HIF-1α)、血管内皮生长因子(VEGF)。结果:鼠G422脑胶质瘤脑部及腋部皮下移植瘤,空白、单注药和单照光三组对照组之间缺氧诱导因子(HIF-1α)、血管内皮生长因子(VEGF)表达值两两比较,P>0.05,差别无统计学意义。不同剂量HPPH、HpD光敏剂PDT治疗鼠G422脑胶质瘤脑部移植瘤,HIF-1α、VEGF平均值,HPPH-PDT各组较HpD-PDT低,0.3mg/kg-PDT组、0.45mg/kg-PDT组低于0.15mg/kg-PDT组及HpD-PDT组,P<0.05,有显著差异。HPPH-PDT 0.3mg/kg-PDT组、0.45mg/kg-PDT二组值接近。HPPH-PDT 0.3mg/kg-PDW组、0.45mg/kg-PDT接近正常脑值,0.15mg/kg-PDT及HpD-PDT组稍高于正常脑值,但P>0.05,无显著差异,HPPH-PDT各组及HpD-PDT组值均明显低于对照组(空白组、单注HPPH、单注射HpD组、单665nm激光照射组、单630nm激光照射组),P值<0.05,有显著差异。各组肿瘤边缘的值稍高于肿瘤值,血液的值较肿瘤低,接近或稍高于正常脑值。不同剂量HPPH、HPD光敏剂PDT治疗鼠G422胶质瘤腋部皮下移植瘤HIF-1α、VEGF平均值,HPPH-PDT各组较HpD-PDT低,0.3mg/kg-PDT组、0Objective： The expression of HIF-1α and VEGF of mice g422 glioma brain and subcutaneous axillary tumors in response to HPPH-PDT was evaluated. The comparison of effect of HPPH-PDT and HpD-PDT was assessed. Methods： The mice G422 glioma model in brain and subcutaneous axillary tumors was established. Mice suffering G422 glioma were randomly divided into seven groups： blank control,HPPH 0.45 mg/kg alone,665nm laser alone,HPPH-PDT （0.15 mg/kg,0.3 mg/kg,0.45 mg/kg ）and HpD-PDT5mg/kg. Mice were injected intravenously with 0.15,0.3,0.45 mg/kg of HPPH utilizing 665nm diode laser doses of 204 J/cm^2 at 200mW/cm^2 delivered at 24 hours post drug injection for HPPH-PDT groups. For HpD-PDT group, 24 hours after intravenous injection of HpD 5 mg/kg, 630 nm diode laser doses of 240 J/cm^2 at 200 mW/cm^2 was given. The expression of HIF-1α and VEGF of mice g422 glioma （tumor , edge of tumor, blood ） was tested on the ninth day post PDT by enzyme-linked immunosorbent assay （ELISA）. Results： No significant difference of expression of HIF-1α and VEGF among blank control group,HPPH0.45mg/kg alone group and 665 nm laser alone group. Compared with blank control group, expression of HIF-1α and VEGF of HPPH-PDT groups significantly decreased, P〈0.01. Expression of HIF-1α and VEGF of HPPH-PDT 0.3 mg/kg and 0.45mg/kg group was lower than that of 0.15 mg/kg group obviously, P〈0.05. No significant difference between 0.45 mg/kg group and 0.3 mg/kg group, P〉0.05. Expression of HIF-1α and VEGF of HPPH-PDT 0.3 mg/kg group decreased in comparison with HpD-PDT group. Conclusion： HPPH-PDT induced decrease HIF-1α and VEGF expression. Appropriate dose was 0.3 mg/kg. Expression of HIF-1α and VEGF of HPPH-PDT was lower than that of HpD-PDT.

关 键 词：HPPH 光动力治疗 HpD G422脑胶质瘤 缺氧诱导因子(HIF-1α) 血管内皮生长因子(VEGF) 

分 类 号：R73[医药卫生—肿瘤]