超声纳米微泡联合阿霉素对小鼠H22移植瘤治疗及毒性的探讨  

The exploration on the therapy and toxicity of adriamycin on H22 transplantation mice combined with ultrasound nano/microbubbles

作　　者：刘娜[1] 陈云超[1] 肖婷[1] 仇春丽 

机构地区：[1]华中科技大学同济医学院附属同济医院超声影像科,武汉430030

出　　处：《中华超声影像学杂志》2016年第8期723-726,共4页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金面上项目（30970882）

摘　　要：目的探讨超声纳米微泡是否能减少阿霉素治疗小鼠H22移植瘤的剂量及降低对小鼠的心脏毒性。方法将30只已建立皮下H22移植瘤模型的昆明雌鼠随机分为5组，即对照组、阿霉素1．0mg／kg、阿霉素1．5mg／kg、阿霉素2．5mg／kg组及1．0mg／kg阿霉素＋微泡＋超声组，每组6只，隔天治疗1次，治疗5次。用超声监测皮下肿瘤的生长情况，绘制肿瘤生长曲线图，治疗后取肿瘤组织切片，进行HE染色及CD34、ki67免疫组化染色，观察肿瘤细胞坏死情况，计数肿瘤组织微血管密度，对肿瘤细胞增殖活性进行定量，测定小鼠血清的肌酸激酶（CK）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH），评价各组处理对肿瘤的抑制作用以及毒性作用。结果与对照组相比，其他各组肿瘤生长延缓，肿瘤坏死面积增加，微血管密度（MVD）减少，增殖期肿瘤细胞数减少（P〈0，05），1．0mg／kg阿霉素＋微泡＋超声组的肿瘤体积、MVD值及增殖期肿瘤细胞数均显著小于除了2．5mg／kg阿霉素组外的其他各组（Pd0．05）。1．0mg／kg阿霉素＋微泡＋超声组小鼠血清的AST、CK、LDH值均低于2．5mg／kg阿霉素组（P〈0．05），与1．5mg／kg阿霉素组相比仅CK值低于后者（P=0．002）。结论超声微泡与阿霉素联合应用可减少阿霉素对小鼠H22移植瘤的治疗剂量，在确保治疗效果的同时减少了化疗药的毒性。Objective To investigate whether ultrasound mediated nano/microbubbles（NMB） could reduce the dosage and cardiotoxicity of adriamycin （ADM） on the treatment of H22 transplanted mice model. Methods Thrity models of transplanted subcutaneously tumors in female KM mice were randomly divided into 5 groups（ n = 6） ： the control group, ADM 1.0 mg/kg, 1.5 mg/kg, 2.5 mg/kg groups and 1.0 mg/kg ADM ＋ NMB ＋ US group. The mice were treated every other day for five times. After treatment the mice were sacrificed and the growth of the tumor was monitored by ultrasound and drawn tumor growth curve diagram. The tumor was extracted for HE staining, CD34 and ki67 immumobistochemical staining to observe and count the necrosis area, the microvascular density and the proliferation of tumor cells. The myocardial enzymes （AST, CK, LDH） were assayed to evaluate the cardiac toxicity of each treatment in mice. Results Compared with the control group, the all experiment groups were with a tumor growth slowly,necrosis area enlargement, mierovascular density and the tumor cell proliferating phase decreased （P〈0.05）. The tumor＇s volume, microvascular density and the tumor cell proliferating phase in the 1.0 mg/kg ADM ＋ NMB ＋ US group were less than those in other groups （ P 〈0.05） expect for 2.5 mg/kg ADM group（ P 〈0.05）. The values of AST, CK and LDH in 1.0 mg/kg ADM＋ NMB＋ US group were less than those in 2.5 mg/kg ADM group（ P 〈0.05）. The CK in 1.0 mg/kg ADM ＋ NMB ＋ US group was less than that in 1.5 mg/kg ADM group（ P = 0. 002）. Conclusions Ultrasound irradiation combined with nano/microbubbles can keep the therapeutic effect of adriamycin but decrease its dose and toxicity onH22 transplanted mice.

关 键 词：超声空化效应 微气泡 阿霉素 移植肿瘤 微血管密度 心肌酶 

分 类 号：R730.5[医药卫生—肿瘤] R454.3[医药卫生—临床医学]