应用激光, 2012, 32 (3): 251, 网络出版: 2012-08-09  

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-1α and VEGF of Mice G422 Glioma in Response to HPPH-Based Photodynamic Therapy
作者单位
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
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 0.45 mg/kg组、单665 nm激光照射组、单630 nm激光照射组、HPPH-PDT组(0.15、0.3、0.45 mg/kg组)、HpD-PDT 5 mg/kg组。单注射HPPH组、HPPH-PDT组和HpD-PDT组自尾静脉推注入光敏剂, 24 h后以波长665 nm的半导体激光照射HPPH-PDT组和单激光组肿瘤, 功率密度200 mW/cm2, 每光斑照射17 min, 能量密度为204 J/cm2; 以波长630 nm的半导体激光照射HpD-PDT组肿瘤, 功率密度200 mW/cm2, 每光斑照射20 min, 能量密度为240 J/cm2。于PDT后9 d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, 0.3 mg/kg-PDT组、0.45 mg/kg-PDT组低于0.15 mg/kg-PDT组及HpD-PDT组, P<0.05, 有显著差异。HPPH-PDT 0.3 mg/kg-PDT组、0.45 mg/kg-PDT二组值接近。 HPPH-PDT 0.3 mg/kg-PDT组、0.45 mg/kg-PDT接近正常脑值, 0.15 mg/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, 0.3 mg/kg-PDT组、0.45 mg/kg-PDT组低于0.15 mg/kg-PDT组及HpD-PDT组, P<0.05, 有显著差异, HPPH-PDT 0.3 mg/kg-PDT组、0.45 mg/kg-PDT二组值接近。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HpD对侧未治疗组、单665 nm激光照射组、单630 nm激光照射组), 且P<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。结论: HPPH-PDT能诱导缺氧诱导因子(HIF-1α)、血管内皮生长因子(VEGF)表达降低, 与HpD-PDT相比, 表达更低。HPPH-PDT疗效优于HpD-PDT, 本实验条件下HPPH-PDT 0.3 mg/kg是较合适的光敏剂剂量。
Abstract
Objective: 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/cm2 at 200mW/cm2 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/cm2 at 200 mW/cm2 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-α 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-α 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.

王宇, 朱菁, 张慧国, 张美珏, 施虹敏. 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[J]. 应用激光, 2012, 32(3): 251. Wang Yu, Zhu Jing, Zhang Huiguo, Zhang Meijue, Shi Hongmin. Research on Expression of HIF-1α and VEGF of Mice G422 Glioma in Response to HPPH-Based Photodynamic Therapy[J]. APPLIED LASER, 2012, 32(3): 251.

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