二氧化锆纳米颗粒荷载阿霉素经不同途径给药治疗兔VX2肝移植瘤  

Zirconium dioxide nanoparticle loaded doxorubicin administered through different ways for treatment of hepatic VX2 transplanted tumor in rabbit models

作　　者：赵璠[1] ZHAO Fan(Department of Ultrasound,Shengjing Hospital of China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属盛京医院超声科,辽宁沈阳110001

出　　处：《中国介入影像与治疗学》2019年第5期299-303,共5页Chinese Journal of Interventional Imaging and Therapy

摘　　要：目的比较经不同途径给药后载阿霉素(DOX)的二氧化锆纳米颗粒及游离DOX兔VX2肝移植瘤生长情况及药物靶向性。方法建立兔VX2肝移植瘤模型25只,随机分为5组,A组经肝动脉给予载DOX二氧化锆纳米颗粒,B组外周静脉给予载DOX二氧化锆纳米颗粒,C组经肝动脉给予游离DOX,D组经外周静脉给予游离DOX,E组为空白对照组。通过CT检查测量给药后1、3、6天各组同期肿瘤体积,分别计算各组3天与1天、6天与3天、6天与1天肿瘤体积比。多组间肿瘤体积比比较采用单因素方差分析,两两比较采用LSD法或SNK法。对给药后各组模型的离体心脏标本进行组织学观察,评价药物的心脏毒性。结果各组间给药后3天与1天肿瘤体积比、6天与3天肿瘤体积比差异均无统计学意义(F=2.056、1.906,P=0.125、0.149);而各组间给药后6天与1天肿瘤体积比差异有统计学意义(F=4.230,P=0.012),A组明显低于其他组(P均<0.05),且除B组与E组外,B、C、D、E组间两两比较差异均无统计学意义(P均>0.05)。组织学检查显示,A组及B组心肌几乎无损伤或损伤较轻,而C组及D组心肌损伤均较重。结论纳米药物载体与传统介入超选择性肝动脉化疗相结合,可更好地延缓兔VX2肝移植瘤生长,提高药物靶向性,且有助于降低DOX造成的心脏毒性。Objective To compare tumor growth and drug targeting of zirconium dioxide nanoparticles loaded doxorubicin (DOX@ZrO2 ) and free doxorubicin (DOX-Free) administered through different routes of hepatic VX2 transplanted tumor in rabbit models.Methods A total of 25 rabbit models of hepatic VX2 transplanted tumor were established and randomly divided into 5 groups,including group A (DOX@ZrO2 via hepatic artery),group B (DOX@ZrO 2 via peripheral vein),group C (DOX-free via hepatic artery),group D (DOX-free via peripheral vein) and group E (untreated group).Tumor volumes were measured with CT scanning 1 day,3 days and 6 days after drug administration,and the ratio of tumor volume were compared between 3 days and 1 day,6 days and 3 days,as well as 6 days and 1 day. One-way ANOVO analysis was used for multi-group comparison and LSD or SNK method was used for pairwise comparison.Histological observations of isolated heart specimen were performed to evaluate the cardiotoxicity of the drug in each group.Results There was no statistic difference of tumor volume ratio between 3 days and 1 day,nor between 6 days and 3 days ( F =2.056,1.906,P =0.125,0.149),while statistic difference of tumor volume ratio was found between 6 days and 1 day after drug administration ( F =4.230,P =0.012).The tumor volume ratio in group A was significantly lower than that in the other groups ( P <0.05).There was no statistic difference of pairwise comparison among B,C,D and E groups (all P >0.05) except between group B and E.Histological observation showed that the myocardium of group A and group B was just a little or no damage,while of group C and group D were severe damaged.Conclusion Combining traditional super selective hepatic arterial chemotherapy targeting surgical treatment method with nano drug carrier,tumor growth of hepatic VX2 transplanted tumor in rabbit model can be delayed,and the drug targeting can be improved.Moreover,the cardiotoxicity caused by doxorubicin can be effectively reduced.

关 键 词：肝肿瘤 兔 二氧化锆纳米颗粒 阿霉素 药物释放系统 

分 类 号：R-332[医药卫生] R445.1