中药康莱特联合放化疗对Lewis肺癌小鼠的抑瘤作用及机制  

Effect and mechanism of a Chinese medicine Kanglaite combined with chemoradiotherapy on Lewis lung cancer mice

作　　者：姚健[1] 信红亚 曾贵荣[2] 石镇港 吴莉峰 徐永兴 袁湘中 王平 YAO jian;XIN Hong-ya;ZENG Gui-rong;SHI Zhen-gang;WU Li-feng;XU Yong-xing;YUAN Xiang-zhong;WANG Ping(Jilin Provincial People′s Hospital,Changchun 130021,China;Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs&Hunan Provincial Research Center for Safety Evaluation of Drugs,Changsha 410331,China;Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]吉林省人民医院,吉林长春130021 [2]湖南省药物安全评价研究中心暨新药药效与安全性评价湖南省重点实验室,湖南长沙410331 [3]中南大学湘雅医院,湖南长沙410008

出　　处：《中国药理学与毒理学杂志》2019年第11期956-962,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：湖南省科技厅重点研发计划(2017NK2282)。

摘　　要：目的研究中药康莱特注射液(KI)或康莱特胶囊(KC)联合放化疗对Lewis肺癌小鼠的抑瘤作用及机制。方法雄性C57BL/6小鼠96只,其中84只背部接种Lewis肺癌细胞,瘤体积达到200 mm^3且无破溃时,按瘤体体积兼顾体质量分为7组,分别为:荷瘤模型组、放疗组(Rad)、放疗+5 d顺铂2 mg·kg^-1组(Rad+Cis×5)(iv给药)、放疗+5 d KI组(Rad+KI×5)、放疗+5 d KI+11 d KC 1.4 g·kg^-1组(Rad+KI×5+KC×11)、放疗+16 d KI组(Rad+KI×16)、放疗+顺铂2.0 mg·kg^-1+5 d KI+11 d KC组(Rad+Cis+KI×5+KC×11),KI均按13 mL·kg^-1 iv给予,KC按1.4 g·kg^-1 ig给予。另取12只C57BL/6小鼠作为正常对照组,除正常对照组外,其余小鼠采用225 Cx放疗系统进行瘤体放疗,放疗强度为2 Gy·d^-1,连续照射5 d,给药期间测量瘤大小,计算瘤体积。末次给药后解剖取瘤组织称重,计算肿瘤抑制率。16 d后,血液生化仪检测白细胞(WBC)、红细胞(RBC)计数、血红蛋白(Hgb)含量,流式细胞仪检测外周血CD3^+CD4^+和CD3^+CD8^+T淋巴细胞亚群百分比,骨髓涂片观察巨核细胞、红细胞系和粒细胞系变化,取胸腺、脾称重,计算脏器指数,并对胸腺、脾进行组织病理学观察。结果Rad+Cis+KI×5+KC×11组小鼠死亡率明显低于Rad组(P<0.05);明显降低给药第6~15天瘤体积(P<0.01),且明显低于Rad组和Rad+Cis×5组第12~15天瘤体积(P<0.01);能明显降低小鼠瘤重(P<0.01),且明显低于Rad组和Rad+Cis×5组(P<0.05);对骨髓造血抑制具有明显的修复作用,明显升高小鼠RBC数量和Hgb含量,能增加小鼠骨髓有核细胞(P<0.01),明显增加小鼠胸腺指数,降低脾指数(P<0.05),升高小鼠外周血T淋巴细胞亚群CD3+CD4+百分比(P<0.05),且对免疫器官胸腺和脾无明显副作用。结论KI或KC联合放化疗对Lewis肺癌小鼠具有增效抑瘤、增效减毒作用,其作用机制与增强免疫有关。OBJECTIVE To investigate the tumor-suppressing effect and mechanism of Kanglaite injection(KI)or Kanglaite capsule(KC)combined with chemoradiotherapy in increasing radiation toler?ance of Lewis lung cancer mice.METHODS Totally 84 tumor-bearing mice with tumor size over 200 mm^3 were selected and divided into seven groups according to tumor size and mass:tumor-bearing model group,radiotherapy(Rad)group,Rad+cisplatin 2 mg·kg^-1(Rad+Cis)group,Rad+5 d KI 13 mL·kg^-1(Rad+KI×5)group,Rad+5 d KI 13 mL·kg^-1+11 d KC 1.4 g·kg^-1(Rad+KI×5+KC×11)group,Rad+KI×16 group,and Rad+Cis+KI×5+KC×11 group.The tumor-bearing mice underwent radiation therapy at an intensity of 2 Gy per day.The tumor size was measured and tumor volume was calculated.After the last dose,red blood cell(RBC),hemoglobin(Hgb)and white blood cell(WBC)tests were performed.The peripheral blood T lymphocyte subsets CD3^+CD4^+ and CD3^+ CD8^+ percentage was of these mice was detected by flow cytometry.RESULTS The mortality of Rad+Cis+KI×5+KC×11 group was signifi?cantly lower than that of Rad group(P<0.01).6-15 days after administration,the tumor volume was sig?nificantly reduced(P<0.01),and significantly smaller than that at 12-15 d after treatment in Rad group and Rad+Cis×5 group(P<0.01).The tumor mass of mice was significantly decreased(P<0.01),and was significantly lower than that of Rad group and Rad+Cis×5 group(P<0.05).RBC count and Hgb content were significantly increased in mice,and bone marrow hematopoietic inhibition was effectively repaired by increasing the bone marrow nucleated cells in mice(P<0.01).This approach could significantly increase the thymus index in mice and reduce the spleen index(P<0.05).The peripheral blood T lympho?cyte subsets CD3+CD4+content of these mice was significantly increased(P<0.05).There was no obvious adverse reaction related to such immune organs as the thymus and spleen.CONCLUSION KI and KC combined with chemoradiotherapy can have significant tumor suppressive effect on Lewis lung cancer mice.The mechanism is

关 键 词：康莱特 肺癌 放化疗 

分 类 号：R965[医药卫生—药理学]