阿霉素长循环热敏脂质体联合射频热疗的药效学研究  

Pharmacodynamics of Doxorubicin Long-circulating Thermo-sensitive Liposomes Combined with Radiofrequency Thermotherapy

作　　者：王雪莉[1] 马红岩[1] 

机构地区：[1]商丘医学高等专科学校附属医院妇产科,商丘476005

出　　处：《肿瘤防治研究》2016年第5期350-354,共5页Cancer Research on Prevention and Treatment

摘　　要：目的考察阿霉素长循环热敏脂质体(doxorubicin long-circulating thermo-sensitive liposomes,DOX-LCTSLs)与射频(radiofrequency,RF)热疗联合对人宫颈癌He La荷瘤裸鼠的抗肿瘤效果及相关药效。方法构建人宫颈癌He La荷瘤裸鼠模型,将小鼠随机分为6组:对照组、RF热疗组、DOX组、DOX-LCTSLs组、DOX+RF组和DOX-LCTSLs+RF组。分别在给药0.5 h、4 h及12 h后检测组织中药物的含量,确定DOX在各时间段主要组织及肿瘤中的分布情况;治疗期间观察裸鼠的生活状态,隔天测量肿瘤体积变化并计算抑瘤率;治疗结束后将主要器官及肿瘤切片进行HE染色,观察各组织器官的细胞形态学变化;使用TUNEL染色法考察肿瘤组织细胞凋亡情况。结果组织分布结果表明,DOX-LCTSLs组在心脏分布明显比DOX组减少;DOX-LCTSLs+RF组抑瘤率达82.14%,与DOX组及DOX+RF组相比差异有统计学意义(P<0.05);HE组织切片表明DOX-LCTSLs对裸鼠主要脏器无明显毒性,而肿瘤组织细胞出现不规则及核溶解现象;TUNEL凋亡检测表明,经过DOX-LCTSLs+RF组尾静脉注射治疗后,肿瘤组织出现明显凋亡现象。结论 DOX-LCTSLs与其他治疗组相比,具有明显的热敏控释性、低毒性,联合RF热疗可显著增强DOX抗肿瘤活性。Objective To investigate the tumor inhibiting effects and relative pharmacodynamics of doxorubicin long-circulating thermo-sensitive liposomes（DOX-LCTSLs） combined with radiofrequency（RF） thermotherapy on He La tumor-bearing nude mice. Methods A He La tumor-bearing mice model was established and the mice were divided into six groups： Control, RF, DOX, DOX-LCTSLs, DOX＋RF and DOX-LCTSLs＋RF groups. DOX concentration in the organs and tumor were detected at 0.5, 1, 4 and 12 h to determine the biodistribution. During the treatment, the living conditions of the nude mice were observed, the tumor volume was measured every other day and the tumor inhibition rate was calculated. After the treatment, the organs and tumor were stained by HE, and the morphological changes of the cells were observed. TUNEL stained method was used to detect cell apoptosis effect. Results Biodistribution results indicated that DOX concentration of DOX-LCTSLs group in the heart was significantly lower than that of DOX group; the tumor inhibition rate of DOX-LCTSLs＋RF group was 82.14% which had significant difference compared with DOX and DOX＋RF groups（P0.05）. HE staining results of DOX-LCTSLs group demonstrated that it had no obvious toxicity to major organs, however, the tumor cells appeared irregular and karyolysis; TUNEL apoptosis detection showed that the tumor tissues appeared significant apoptosis after the treatment on DOXLCTSLs＋RF group. Conclusion Compared with other treatment groups, DOX-LCTSLs group have the obvious thermal control release effect and low toxicity. With RF thermotherapy treatment, DOX-LCTSLs could significantly enhance the anti-tumor activity.

关 键 词：长循环热敏脂质体 射频 热疗 阿霉素 

分 类 号：R943[医药卫生—药剂学] R711.7[医药卫生—药学]