应用激光, 2012, 32 (5): 446, 网络出版: 2012-11-28   

HPPH光动力学治疗鼠G422脑胶质瘤的实验研究

Experimental Research on HPPH-PDT in Treatment of G422 Glioma of Mice
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: 通过对鼠G422脑胶质瘤脑及腋部皮下移植瘤模型HPPH光动力学治疗, 从肉眼、肿瘤生长曲线、病理、观察各剂量组疗效, 并与对照组及HpD作对比, 寻找HPPH-PDT治疗鼠G422脑胶质瘤合适的HPPH剂量。方法: 建立鼠G422脑胶质瘤脑及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、单注射HpD组、单665 nm激光照射组、单630 nm激光照射组、HPPH-PDT各组(0.15 mg/kg、0.3 mg/kg、0.45 mg/kg组)、HpD-PDT 5 mg/kg组。单注射HPPH组、HPPH-PDT组和单注射HpD组、HpD-PDT组自尾静脉推注入光敏剂, 24小时后以波长665 nm的半导体激光照射HPPH-PDT组和单665 nm激光照射组肿瘤, 功率密度200 mW/cm2, 每光斑照射17 min, 能量密度为204 J/cm2; 功率密度100 mW/cm2, 每光斑照射34min, 能量密度为204 J/cm2; 以波长630 nm的半导体激光照射HpD-PDT组及单630 nm激光照射组肿瘤, 功率密度200 mW/cm2, 每光斑照射20 min, 能量密度为240 J/cm2。肉眼观察肿瘤外形变化, 测量(治疗前、3、5、7、9 d)肿瘤体积, 于PDT后9 d处死鼠, 取肿瘤、肿瘤边缘、正常脑组织, 作病理检查。结果: 可见未经光动力治疗对照组肿瘤迅速生长,第9天体积平均长至治疗前的4.86~5.97倍, HPPH-PDT 0.3 mg/kg、0.45 mg/kg组与治疗前体积平均比是0.94及0.97倍,HPPH-PDT 0.15 mg/kg组是1.09倍、HpD-PDT组是1.6倍, 光动力学组肿瘤的生长速度明显低于对照组, P值<0.05,有统计学差别, HPPH-PDT 各组优于HpD-PDT组。HPPH-PDT 0.3 mg/kg、0.45 mg/kg组抑瘤效果优于HPPH-PDT 0.15 mg/kg组、HpD-PDT组(P值<0.05,有统计学差别)。HPPH-PDT 0.3 mg/kg、0.45 mg/kg组抑瘤效果相似。在同样能量密度时高功率密度组第9天疗效较低能量密度稍好,但无统计学差别。故由抑瘤效果层面分析HPPH-PDT对鼠G422脑胶质瘤有抑制作用, 并与HPPH剂量相关, 适宜的剂量为0.3 mg/kg; HPPH-PDT对鼠G422脑胶质瘤的抑瘤作用较HpD-PDT强。从病理观察鼠G422脑胶质瘤脑及皮下移植瘤各剂量HPPH-PDT组及HpD-PDT治疗组, 治疗9 d后仅个别标本肿瘤组织及细胞已消失, 大部分肿瘤组织明显变性坏死, 但深部仍有带活性肿瘤细胞, 与对照组成巢状生长大片活性肿瘤细胞有明显差别。且坏死程度, HPPH-PDT组明显优于HpD-PDT组, 0.3 mg/kg、0.45 mg/kgHPPH-PDT组优于0.15 mg/kg HPPH-PDT组, 0.3 mg/kg、0.45 mg/kg HPPH-PDT组两组程度相似, 故0.3mg/kg是较合适的HPPH-PDT光敏剂剂量。结论: 从抑瘤效果、病理分析, HPPH-PDT对鼠G422脑胶质瘤生长有抑制作用, 抑瘤效果与HPPH剂量有关, 适宜的剂量为0.3 mg/kg; HPPH-PDT对鼠G422脑胶质瘤抑瘤效果较HpD-PDT强。
Abstract
Objective: To ascertain the adequate dosage of HPPH of HPPH-PDT in treatment of G422 glioma of mice by vegetal curve of tumor and pathology. 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、665 nm laser alone、630 nm laser alone、HPPH-PDT(0.15 mg/kg、0.3 mg/kg、0.45 mg/kg )and HpD-PDT 5 mg/kg. Mice were injected intravenously with 0.15、0.3、0.45 mg/kg of HPPH utilizing 665 nm diode laser doses of 204 J/cm2 at 200 mW/cm2 delivered at 24 hours post drug injection for HPPH-PDT groups. For HpD-PDT group, 24 hours after intravenous injection of HpD5mg/kg, 630nm diode laser doses of 240 J/cm2 at 200 mW/cm2 was given. Research on inhibition efficacy of tumors of mice G422 Glioma by HPPH-based photodynamic therapy from vegetal curve of tumor and pathology. To ascertain the adequate dosage of HPPH and time of treatment of HPPH-PDT in treatment of G422 glioma of mice, the comparison of effect of HPPH-PDT and HpD-PDT was assessed. Results: The contrary control groups was 4.86~5.97 times, the HPPH-PDT 0.3 mg/kg and 0.45 mg/kg groups was 0.94 times and 0.97 times, HPPH-PDT 0.15 mg/kg groups was 1.09 times、HpD-PDT groups was 1.6 times after treatment by PDT in treatment of G422 glioma of mice at ninth day than that before the treatment of tumors volume. The increase degree of tumors volume of PDT side was obviously less than that of the contrary control side, P<0.05. The increase degree of tumor volume of HPPH-PDT 0.3 mg/kg and 0.45 mg/kg group was obviously less than that of the 0.15mg/kg group and HpD-PDT group, P<0.05. HPPH-PDT 0.3 mg/kg and 0.45 mg/kg group was obviously slightly, P>0.05, less than that of the 0.3 mg/kg group. From the degree of denaturalization putrescence of tumor at pathology, HPPH-PDT group and HpD-PDT group exceeded control group, HPPH-PDT 0.3 mg/kg and 0.45 mg/kg group exceeded 0.15 mg/kg group and HpD-PDT group obviously, 0.45 mg/kg group exceeded 0.3 mg/kg group slightly, HPPH-PDT 0.3 mg/kg exceeded HpD-PDT group obviously. Conclusion: From the observe from vegetal curve of tumor and pathology, the HPPH-PDT can inhibit growth of tumor of G422 glioma in correlation with dose of HPPH. Appropriate dose was 0.3mg/kg. The inhibition effect on G422 glioma by HPPH-PDT was better than HpD-PDT.

王宇, 朱菁, 张慧国, 张美珏. HPPH光动力学治疗鼠G422脑胶质瘤的实验研究[J]. 应用激光, 2012, 32(5): 446. Wang Yu, Zhu Jing, Zhang Huiguo, Zhang Meijue. Experimental Research on HPPH-PDT in Treatment of G422 Glioma of Mice[J]. APPLIED LASER, 2012, 32(5): 446.

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