青藤碱PLGA-TPGS纳米粒对HCa-F细胞在小鼠淋巴管内增殖及异位移植瘤的抑制作用研究  

Study on Inhibitory Effects of Sinomenine-loaded PLGA-TPGS Nanoparticles on the Proliferation of HCaF Cells in Lymph Tubes and Ectopic Transplantation Tumors in Mice

作　　者：王洪刚[1] 高萌[2] 张成鸿[3] 徐静[3] 孙艺平[3] 徐红[3] 

机构地区：[1]大连医科大学附属第一医院药剂科,辽宁大连116011 [2]大连医科大学药学院,辽宁大连116044 [3]大连医科大学基础医学院,辽宁大连116044

出　　处：《中国药房》2016年第16期2229-2232,共4页China Pharmacy

摘　　要：目的:研究青藤碱乳酸羟基乙酸共聚物-水溶性维生素E(PLGA-TPGS)纳米粒(SPTN)对小鼠腹水型肝癌高淋巴管转移细胞HCa-F在小鼠淋巴管内增殖及异位移植瘤的抑制作用。方法:将HCa-F细胞悬液分别加入生理盐水、5-氟尿嘧啶溶液(FS)、青藤碱溶液(SS)、青藤碱PLGA纳米粒(SPN)和SPTN,使终质量浓度均为80μg/ml,采用羧基荧光素琥珀酰亚胺酯(CFSE)标记;经小鼠一侧足垫注射各细胞悬液50μl,每组15只,分别于3、6、9、12、24 h用荧光倒置显微镜观察上述悬液对HCa-F细胞在小鼠体内淋巴管内增殖的抑制作用。取小鼠分为正常对照组、空白PLGA-TPGS纳米粒(EPTN)组、生理盐水组、SPTN组、SPN组、SS组和FS组,每组10只,后6组小鼠建立荷HCa-F细胞的肝癌异位移植瘤模型,尾iv相应药物15 mg/kg,每日1次,连续给药10 d;检测血清中丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(γ-GT)、白蛋白(ALB)和总胆红素(TBIL)的含量;取出实体瘤,称量瘤质量和瘤体积,计算抑瘤率。结果:对HCa-F细胞增殖的抑制作用强弱依次为SPTN>SPN>FS>SS>生理盐水。与生理盐水组比较,SPTN组、SPN组、SS组和FS组小鼠血清中ALT、AST、γ-GT、TBIL水平降低,ALB水平升高(P<0.05);SPTN组、SPN组和FS组小鼠的瘤体积增长量和瘤质量明显降低(P<0.05),抑瘤率依次为49.62%、40.53%、33.90%。结论:SPTN可抑制HCa-F细胞在小鼠淋巴管内的增殖,能改善荷HCa-F细胞小鼠肝癌异位移植瘤,且效果优于SPN和FS。OBJECTIVE：To study the inhibitory effects of sinomenine（SIN）-loaded polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate（PLGA-TPGS）nanoparticles（SPTN）on the proliferation of HCa-F cells in lymph tubes and ectopic transplantation tumors in mice.METHODS：HCa-F cell suspension were incubated with normal saline,5-fluorouracil（FS）,sinomenine solutions（SS）,sinomenine PLGA nanoparticles（SPN） and SPTN,with concentration of 80 μ g/ml.The cells were marked with CFSE,and then were injected with suspension 50 μl via one footpad of mice.Inhibitory effect of above suspensions on the proliferation of HCa-F in lymph tubes of mice was observed by fluorescence inverted microscope at 3,6,9,12,24 h（n=15）.Mice were divided into normal control group,blank PLGA-TPGS nanoparticles（EPTN）group,normal saline group,SPTN group,SPN group,SS group and FS group with 10 mice in each group.The latter 5 groups were injected with relevant medicine15 mg/kg,once a day,via tail vein for consecutive 10 days after the model of HCa-F cells-bearing ectopic transplantation tumor mice was established.The serum content of ALT,AST,γ-glutamyltransferase（γ-GT）,ALB and T-BIL were determined;solid tumors were taken,measured and weighed,and the inhibitory rate of tumor was also calculated.RESULTS：The inhibitory effect of above solution on the proliferation of HCa-F cells in descending order was as follows：SPTN〉SPN〉FS〉SS〉normal saline.Compared with normal saline group,the serum levels of ALT,AST,γ-GT and TBIL of SPTN group,SPN group,SS group and FS group decreased,while ALB level increased（P〈0.05）;the amount of tumor volume increase and tumor weight in SPTN group,SPN group and FS group decreased significantly（P〈0.05）.The inhibitory rate of tumor in 3 groups were 49.62%,40.53% and33.90%.CONCLUSIONS：SPTN can inhibit the proliferation of HCa-F cells in lymph tubes of mice,and can improve HCa-F cells-bearing ectopic transplantation tumor in mice.It is better than SPN and FS.

关 键 词：青藤碱 乳酸羟基乙酸共聚物-水溶性维生素E 纳米粒 HCa-F细胞 淋巴管 异位移植瘤 

分 类 号：R285[医药卫生—中药学]