华卟啉钠介导的声动力疗法联合声诺维促脑胶质瘤凋亡的体内外实验研究  

Experimental Study on the Effect of Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Combined with SonoVue on Glioma Apoptosis in Vivo and in Vitro

作　　者：赵睿[1] 姜欢[1] 戴绍春[1] ZHAO Rui;JIANG Huan;DAI Shaochun(Department of Ultrasound,Cancer Hospital of Harbin Medical University,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学附属肿瘤医院超声科,黑龙江哈尔滨150081

出　　处：《中国医学影像学杂志》2022年第12期1201-1205,1211,共6页Chinese Journal of Medical Imaging

基　　金：黑龙江省博士后科研发展基金资助项目(LBH-Q15103)。

摘　　要：目的 探讨华卟啉钠介导的声动力疗法(SDT)联合声诺维对脑胶质瘤的凋亡作用。材料与方法 将体外培养的C6胶质瘤细胞随机分为对照组、华卟啉钠组、超声组、超声联合微泡组、SDT组和声动力联合微泡组(SDT-MB组),治疗后采用电子自旋共振法检测活性氧的产生。将建模后的C6胶质瘤荷瘤大鼠同样随机分为6组,每组20只,治疗后采用Tunel染色检测细胞凋亡率,透射电镜观察细胞形态学变化,免疫组化检测Caspase-9、Caspase-3、CD31、Claudin-5、Caveolin-1的表达和Cyt-c的释放,记录6组荷瘤大鼠的生存期。结果 与其他4组相比,SDT组和SDT-MB组检测到单线态氧的产生。与其他实验组相比,SDT-MB组荷瘤大鼠胶质瘤细胞的凋亡率最高[(37.10±0.77)%,F=2.35,P<0.05],细胞形态学改变最为明显,并且存活时间显著延长[(29.60±4.45)d,F=12.65,P<0.05];免疫组化结果显示SDT-MB组Caspase-9、Caspase-3、Claudin-5表达、Cyt-c释放显著上调,Caveolin-1、CD31表达显著下调。结论 华卟啉钠介导的声动力疗法联合声诺维可在体外导致单线态氧的产生,并且能促进荷瘤大鼠脑胶质瘤凋亡、引起荷瘤大鼠血-脑屏障发生破坏、延长荷瘤大鼠的生存时间,而且这一凋亡过程与线粒体内源性凋亡途径有关。Purpose To investigate the apoptotic effect of sinoporphyrin sodium(DVDMS)-mediated sonodynamic therapy(SDT combined with SonoVue on glioma. Materials and Methods C6 glioma cells were randomly divided into control group, DVDMS group,ultrasound group, ultrasound combined with microbubble group, SDT group and SDT combined with microbubble(SDT-MB) group. After treatment, electron spin resonance was used to detect the production of reactive oxygen species. Established the tumor model of C6 glioma.The glioma-bearing rats were randomly divided into six groups, 20 rats per group. The apoptotic rate was detected by Tunel staining,morphological change was observed by transmission electron microscopy, and expression of proteins Caspase-9, Caspase-3, CD31, Claudin-5, Caveolin-1 and Cyt-c release were detected by immunohistochemistry. Survival time of six groups of rats was recorded. Results Compared with the other 4 groups, both SDT group and SDT-MB group produced singlet oxygen. Compared with other experimental groups, the apoptosis rate of the SDT-MB group was the highest [(37.10±0.77)%, F=2.35, P<0.05], the cell morphology changed the most, and the survival time of the rats significantly prolonged [(29.60±4.45) d, F=12.65, P<0.05].The expression of Caspase-9, Caspase-3, Claudin-5 and the release of Cyt-c were up-regulated, and Caveolin-1 and CD31 were down-regulated. Conclusion The results suggested that the DVDMS-SDT with SonoVue can cause the production of singlet oxygen in vitro. And it can promote the apoptosis of glioma cells, cause the destruction of the blood-brain barrier, and prolong the survival time of glioma-bearing rats. The pathway is associated with mitochondrial apoptosis.

关 键 词：胶质瘤 超声检查 声动力疗法 华卟啉钠 微泡 

分 类 号：R445.1[医药卫生—影像医学与核医学] R739.41[医药卫生—诊断学]