超声辐照结合载替莫唑胺纳米粒凝胶间质化疗在胶质瘤术后大鼠模型中的实验研究  

Combination of ultrasound irradiation and temozolomide-loaded hydrogel nanoparticle in interstitial chemotherapy after surgical resectionin rat C6 glioma models

作　　者：李一鸣[1] 张海娴[1] 王意达[1] 汪晓虹[1] 王怡[1] 

机构地区：[1]复旦大学附属华山医院超声医学科,上海200040

出　　处：《中华全科医学》2016年第6期907-910,共4页Chinese Journal of General Practice

基　　金：上海市自然科学基金(134119a1300)

摘　　要：目的研究超声辐照结合载替莫唑胺纳米粒凝胶系统间质化疗胶质瘤大鼠术后模型的疗效,探究超声能否增强间质化疗疗效。方法 1选取15只大鼠胶质瘤术后模型,瘤腔注入载荧光素纳米凝胶,做超声辐照结合载荧光素纳米凝胶在术后瘤周脑组织中的弥散实验,随机分为3组,分别进行无超声辐照和2种不同强度超声辐照,术后第7天将全部大鼠灌注取脑制作冰冻切片,荧光显微镜下选取不同部位摄片,观察荧光分布情况,并对不同部位荧光强度进行半定量,分析荧光强度差异。2选取24只大鼠胶质瘤模型进行生存实验:随机分为4组,分别为对照组、手术组、手术+间质化疗组、手术+间质化疗+超声组,记录其死亡时间,进行生存分析。结果 1无超声辐照,载荧光素纳米粒主要集中于瘤腔周围,经超声辐照后,载荧光素纳米粒主要集中于交界处,且远端脑组织内浓度增多。2生存分析显示治疗组与对照组生存时间差异有统计学意义(P<0.05),手术+间质化疗+超声组效果最好。结论超声辐照可促进凝胶中纳米粒向瘤周组织弥散,超声辐照结合载TMZ m PEG-PLGA纳米颗粒凝胶系统间质化疗可显著提高术后胶质瘤大鼠模型的生存时间。Objective To study the therapeutic effect of the combination of ultrasound irradiation and temozolomide-loaded hydrogel nanoparticle in the interstitial chemotherapy after surgical resection in a rat C6 glioma model,to observe the role in enhancing the effect of interstitial chemotherapy. Methods 115 Wistar glioma rats after surgical resection were applied to test the diffusion of fluorescein-loaded hydrogel nanoparticles around the tumor cavity combined with ultrasound irradiation. The tumor residual cavity was filled with fluorescein-loaded hydrogel nanoparticle,divided randomlyinto three groups（ n = 5） ： no ultrasound group and ultrasound irradiation groups respective with 1 MHz 1 min 0. 5 W / cm2 and 1 MHz1 min 1 W / cm2,on the seventh day,the brain tissues were collected and made frozen sections. The distribution of fluorescence were observed and photographed by fluorescence microscope,the fluorescence intensity was measured,and the difference offluorescence intensity was analyzed. 224 Wistar glioma rats were divided into four groups（ n = 6） randomly：Control group,operation group,operation ＋ interstitial chemotherapy group,operation ＋ interstitial chemotherapy ＋ ultrasound group. The survival curves were obtained through the Kaplan-Meier method. Results In no ultrasound group,the fluorescein-loaded nanoparticle concentrated around the tumor cavity,and in ultrasound irradiation group,the fluoresceinloaded nanoparticle concentrated in the adjacent region,and diffused in the further brain tissue more effective. The survival difference among the therapeutic groups or compared with the control group was all statistically significance. Conclusion Ultrasound irradiation can enhance the diffusion of nanoparticle in hydrogel around the tumor cavity; ultrasound irradiation combined with interstitial chemotherapy containing temozolomide-loaded hydrogel nanoparticle will prolong the survival time of C6 glioma rat model after the surgical resection.

关 键 词：超声 间质化疗 胶质瘤 纳米粒 凝胶 

分 类 号：R739.41[医药卫生—肿瘤] R730.58[医药卫生—临床医学]