超声介导自制纳米泡联合顺铂对小鼠H22肿瘤抑制作用的研究  

The experimental study of the inhibitory effect of self-made nanobubbles combined with cisplatin mediated by ultrasound on H22 neoplasms of mice

作　　者：仇春丽 陈云超[1] 刘娜[1] 肖婷[1] 

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2期173-177,共5页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金面上项目（30970882）

摘　　要：目的探讨超声介导自制纳米泡对小鼠皮下H22肿瘤抑制效果最佳的治疗参数，超声辐照自制纳米泡联合顺铂对小鼠皮下H22肿瘤抑制效果及其可能的机制。方法建立30只小鼠H22肿瘤皮下移植瘤模型，随机分为6组，按照治疗方案的不同应用超声联合自制纳米泡对肿瘤予以不同超声强度和时间，在治疗前、治疗后即刻、治疗后24h及72h行超声造影检查及声学定量分析，以超声造影增强强度及微血管密度表达定量评价其疗效，筛选出较理想的超声治疗参数后，再以超声介导微泡联合顺铂治疗肿瘤，观察肿瘤生长情况，计算抑瘤率，以CD31染色作为微血管密度（microvascular density，MVD）表达的定量检测指标，用细胞核相关抗原（KI-67）染色检测肿瘤细胞的增殖情况。结果各条件组肿瘤治疗后各时刻超声增强强度与对照组相比差异有统计学意义（P〈0．05），且随着治疗功率的增强和辐照时间的延长，对小鼠肿瘤的抑制作用越显著，但不良反应也明显增多;联合药物的实验中，除单纯超声组外，各组的肿瘤抑瘤率、微血管计数、KI-67表达与对照组相比差异有统计学意义（P〈o．05），以超声微泡联合药物组肿瘤抑瘤率最大（抑瘤率为70．01％），MVD及肿瘤细胞增殖指数（KI-67LI）最低。结论超声联合自制纳米泡抑制肿瘤生长效果较理想的参数为辐照强度为1W／cm^2，辐照时间1min或3min间歇辐照模式；超声微泡联合药物具有协同抗肿瘤效应，其机制可能是通过抑制肿瘤新生血管生成和诱导肿瘤细胞凋亡而发挥抗肿瘤作用。Objective To investigate the optimal ultrasound exposure parameter on H22 neoplasms of mice meditated by ultrasound exposure combined with self-made nanobubbles, and then observe their therapeutic effect combined with cisplatin and their possible mechanism of anti-tumor. Methods Thirty mice engrafts models with subcutaneous H22 neoplasms were established and divided into 6 groups randomly, which received ultrasound exposure at different intensity and exposure time. The contrast enhanced ultrasound imaging （CEUS） was performed in every group at the four time points of before treatment and at 0 h, 24 h, 72 h after treatment. To obtain the optimal ultrasound parameters, the tumor inhibitory effect was assessed by enhanced intensity （EI） and microvascular density （MVD）. The H22 tumor were treated by ultrasound exposure nanobubbles combined with cisplatin to observe their tumor growth inhibition rate, and the microvessels density and nuclear associated antigen Ki-67 proliferation index were measured by immunohistochemical staining. Results There was a statistically difference in enhanced intensity （El） between the experimental groups and control group （P 〈0.05）. With the increasing of ultrasound intensity and exposure time, the tumor inhibitory effect was more obvious, with an increasing side reactions. Except the simple ultrasound group, there was a statistical difference in tumor inhibition, the mean MVD and the tumor cell proliferation index （KI-67） between control group and the other ultrasound therapy groups （P 〈0.05）. The tumor inhibitory rate was the highest （tumor inhibition rate 70. 0%） and the mean MVD and KI-67 expression were the lowest （ P d0.05） in the combination group comparing with the others. Conclusions The ideal ultrasound exposure parameter of tumor inhibition showed that exposure intensity chose 1 W/cm2 and exposure time chose 1 min or 3 rain intermittence. The ultrasound exposure self-made nanobubbles combined with cisplatin could enhance the tumor inhibit

关 键 词：超声检查 微气泡 肝肿瘤 实验性 顺铂 

分 类 号：R445.1[医药卫生—影像医学与核医学] R73-36[医药卫生—诊断学]