HPPH光动力学治疗大鼠C6脑胶质瘤肿瘤生长实验研究的磁共振表现  

Magnetic Resonance Evaluation for C6Glioma Growth after the Photodynamic Therapy with 2-[1-Hexyloxyethyl]-2-Devinyl Pyropheophorbide-Alpha(HPPH)in the C6 Glioma Model of the Rat

作　　者：王宇[1] 沈加林[2] 林勇[1] 张慧国[3] 赵子周[2] 刘桂勤[2] 王磊[1] 朱菁[3] 

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放射科,上海200127 [3]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》2014年第2期149-159,共11页Applied Laser

基　　金：上海市科学技术委员会动物专项资助项目(项目编号:11140900360)

摘　　要：目的:以不同剂量新型光敏剂HPPH光动力学疗法治疗大鼠C6脑胶质细胞瘤模型,通过磁共振平扫及增强扫描来测定各组肿瘤的大小,绘出生长曲线,选择最佳的治疗剂量并与传统HPD-PDT(血卟啉光动力学疗法)作对比,并以病理、电镜检查作验证。方法:建立大鼠C6脑胶质细胞瘤模型建立,设立对照组(肿瘤未治疗组、单注射HPPH 0.45mg/kg组、单注射HPD5mg/kg组、单波长667nm激光照射组、单波长630nm激光照射组),光动力学治疗组(HPPH-PDT各组(0.15、0.30、0.45mg/kg组)、HpD-PDT 5mg/kg组)。单注射HPPH 0.45mg/kg组、HPPH-PDT组和单注射HPD 5mg/kg组、HpD-PDT组自尾静脉推注入光敏剂,光动力学组注光敏剂18h后照激光。以波长667nm的半导体激光照射HPPH-PDT组和单667nm激光照射组肿瘤,功率密度200mW/cm2,每光斑照射20min,能量密度为240J/cm2;以波长630nm的半导体激光照射HpDPDT组及单630nm激光照射组肿瘤,功率密度200mW/cm2,每光斑照射20min,能量密度为240J/cm2。肉眼观察鼠行为变化,以磁共振平扫及增强扫描测量治疗前、治疗后第7、14天或对照组肿瘤生长第7、14、21天肿瘤体积,绘制肿瘤生长曲线,于PDT后14天或对照组肿瘤生长21天鼠脑,磁共振增强扫描测量后处死鼠,取脑组织作病理、电镜检查。结果:大鼠PDT治疗后,光动力学治疗组疗效较好的鼠,未出现异常表现,而对照组及光动力学治疗疗效较差组出现大鼠消瘦、萎靡或偏瘫、视盲。所有鼠均未出现皮肤红斑、水肿等光毒性反应。磁共振增强扫描测定肿瘤生长不同时间体积,并绘出肿瘤生长曲线。光动力学治疗前及治疗后14天肿瘤体积比(P14/P0),即肿瘤生长第21天与7天比(T21/T7),HPPH 0.15、0.30、0.45mg/kg-PDT组、HPD5mg/kg-PDT组值为4.43±4.80、0.37±0.25、0.71±0.42、8.31±1.56;对照组单注药HPPH 0.45mg/kg组、单注药HPD5mg/kg组、单激光667nm照射组、单激光630nm照射组、未治疗肿瘤组为17.ObjectiveThe objective is to evaluate the efficacy of the photodynamic therapy （PDT） for the glioma treatment, usingdifferent doses of 2-[-1-hexyloxyethyl]-2-devinyl pyropheophorbide-alpha（HPPH）as a photosensitizer, and find an optimal doseof the HPPH by observing the growth curve of the glioma with magnetic resonance imaging （MRI）, which is then comparedwith traditional hematoporphyrin derivative（HPD）-PDT. Methods：After establishing rat C6 glioma model, the animals were di-vided into nine groups： untreated glioma group, HPPH （0.45 mg/kg） group, HPD （5 mg/kg）, 667 nm laser treated group,630 nm laser treated group, HPPH-PDT groups （0. 15, 0. 30, 0. 45 mg/kg, respectively）, and HPD-PDT（5 mg/kg）group. At18 h after photosensitizers were injected via rat tail vein, while the 667 nm laser at energy density of 240 J/cm2 with a power of200 mW/cm2was used to treat the glioma for 20 min each spot in the HPPH-PDT group and the 667 nm laser treated group, theHPD-PDT group and the 630 nm laser treated group were treated with 630 nm laser. The behaviors of the rat were observed,and the growth curve of the glioma was assessed with MRI before and 7 and 14 d after the treatment. The glioma was taken forpathological and electron microscope examination in 14d post-treatment. Results： After the PDT, some animals have no abnor-mal behaviors, others exhibit reduced body weight, apathy, paralysis, or blindness, but there was no phototoxicity. The rattumor size was measured with enhanced MRI. The ratios of the volume between in P14 animals and in P0 rats were 4.43±4.80,0.37±0. 25, 0. 7±0. 42, and 8. 31±1. 56 in HPPH 0. 15 mg/kg-PDT group, HPPH 0. 30 mg/kg-PDT group, HPPH0.45 mg/kg-PDT group, and HPD 5 mg/kg-PDT group, respectively, while 17.01=[=0. 36, 16.66=[=0.31, 18.37±0.47, 17.66±0.04, and 20. 244-1.75 were noted in the HPPH 0.45 mg/kg group, HPD 5 mg/kg group, 667 nm laser group, 630 lasergroup, and untreated glioma group, respectively. There was a significant difference between the treat

关 键 词：大鼠C6脑胶质细胞瘤 HPPH—PDT 磁共振增强 肿瘤生长曲线 

分 类 号：Q2[生物学—细胞生物学]