咪喹莫特联合高强度聚焦超声治疗小鼠黑色素瘤实验研究  

Experimental Study on Imiquimod Combined with HIFU in the Treatment of Melanoma in Mice

作　　者：陈英华[1] 伍烽[1] W.R.Chen 卫佳[1] 吴丽美[1] 李星星[1] 周兰[1] Chen Yinghua;Wu Feng;W.R.Chen;Wei Jia;Wu Limei;Li Xingxing;Zhou Lan(Department of Biomedical Engineering,Chongqing Medical University,Chongqing Key Laboratory of Biomedical Engineering,Chongqing Key Laboratory of Ul-trasonic Medical Engineering,Co-Construction Cultivation Base of the State Key Laboratory by Province,Chongqing,China 400016;Biomedical EngineeringProgram,Department of Physics and Engineering,College of Math and Science,University of Central Oklahoma,Oklahoma,USA73034)

机构地区：[1]重庆医科大学生物医学工程系·重庆市生物医学工程学重点实验室·重庆市超声医学工程重点实验室--省部共建国家重点实验室培育基地,重庆400016 [2]Biomedical Engineering Program,Department of Physics and Engineering,College of Math and Science.University of Central Oklahoma,USA 73034

出　　处：《中国药业》2018年第12期13-16,共4页China Pharmaceuticals

摘　　要：目的探讨咪喹莫特(imiquimod,IMQ)联合高强度聚焦超声(high intensity focused ultrasound,HIFU)治疗荷B16黑色素瘤小鼠的效果及其机制。方法采用黑色素瘤细胞B16皮下接种小鼠建模,设荷瘤对照组(A组)、IMQ组(B组)、HIFU组(C组)及IMQ联合HIFU组(D组)。观察各组小鼠肿瘤生长情况及小鼠生存时间;制备小鼠脾淋巴细胞,与B16细胞共培养,台盼蓝拒染法检测小鼠脾淋巴细胞对B16细胞的细胞毒性,酶联免疫吸附试验(ELISA)法检测培养上清液中γ干扰素(IFN-γ)和肿瘤坏死因子-α(TNF-α)的水平。结果 A组、B组、C组小鼠中位生存时间分别为29 d,65 d,29 d,均明显短于D组的113 d(P<0.01);A组、B组、C组脾淋巴细胞毒性分别为(23.00±1.73)%,(35.33±5.03)%,(37.50±2.21)%,均明显低于D组的(55.33±7.64)%(P<0.01);A组、B组、C组培养上清液中IFN-γ质量浓度分别为(427.57±42.55)pg/mL,(778.45±27.85)pg/mL,(756.26±81.33)pg/mL,明显低于D组的(965.56±46.29)pg/mL(P<0.01);A组、B组、C组培养上清液中TNF-α质量浓度分别为(278.45±21.72)pg/mL,(399.37±35.29)pg/mL,(365.86±36.95)pg/mL,均明显低于D组的(565.56±46.29)pg/mL(P<0.01)。结论 IMQ联合HIFU治疗能有效延长黑色素瘤小鼠生存期,提高其抗肿瘤免疫功能,其机制可能与Th2向Th1逆转增强有关。Objective To investigate the effect and mechanism of imiquimod（IMQ） combined with high intensity focused ultrasound（HIFU） in the treatment of BALB/c mice bearing B16 melanoma.Methods The B16 melanoma cells were inoculated subcutaneously to establish the models,and the mice were randomly divided into tumor bearing control group（group A）,IMQ group（group B）,HIFU group（group C） and IMQ combined HIFU group（group D）.The volume of tumor and survival time of mice in each group were observed.Splenic lymphocytes were extracted and co-cultured with B16 cells to assess the cytotoxic activity against B16 tumor cells by trypan blue dye exclusion method.Furthermore,the levels of IFN-γ and TNF-α were detected in the supernatant of culture by ELISA.Results The average survival time of groups A（29 d）,group B（65 d） and group C（29 d） were shorter than 113 d in group D（P〈0.01）.The lymphocyte cytotoxicity of group A,group B and group C was（23.00 ± 1.73） %,（35.33 ± 5.03） % and（37.50 ±2.21） %,which was lower than（55.33 ± 7.64） % of group D（P〈0.01）.The levels of IFN-γ of culture supernatant in group A,group B and group C were（427.57 ± 42.55） pg/mL,（778.45 ± 27.85） pg/mL and（756.26 ± 81.33） pg/mL,which were lower than（965.56 ± 46.29） pg/mL in group D（P〈0.01）.The levels of TNF-α of culture supernatant in group A,group B and group C were（278.45 ± 21.72） pg/mL,（399.37 ± 35.29） pg/mL and（365.86 ± 36.95） pg/mL,which were lower than（565.56 ± 46.29） pg/mL in group D（P〈0.01）.Conclusion IMQ combined with HIFU in the treatment of melanoma in mice can effectively prolong the survival time and enhance its anti-tumor immune function.The mechanism may be related to the reverse enhancement of Th2 to Th1.

关 键 词：咪喹莫特 高强度聚焦超声 黑色素瘤 小鼠 免疫 作用机制 

分 类 号：R965.2[医药卫生—药理学] R986[医药卫生—药学]