马钱子碱及其脂质体对移植性肝癌Heps小鼠的抗肿瘤作用和毒性的比较  

Anticancer effect and toxicity of brucine and brucine liposome in mice with transplant Heps tumors in vivo

作　　者：邓旭坤[1] 蔡宝昌[1] 吕晓宇[2] 殷武[3] 王琳[1] 孙靓[1] 

机构地区：[1]南京中医药大学药学院,南京210029 [2]中南民族大学生命科学学院民族药物研究所,武汉430074 [3]南京大学生命科学学院医药生物技术国家重点实验室,南京210093

出　　处：《中国新药杂志》2006年第12期963-967,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金重大研究计划(90209052);江苏省博士创新基金项目(2005098)

摘　　要：目的:比较马钱子碱(brucine,B)和马钱子碱脂质体(brucine liposome,BL)对移植性肝癌Heps小鼠的抗肿瘤作用和毒性。方法:ICR雄性小鼠接种肝癌Heps瘤株造成移植性肝癌Heps小鼠模型(简称Heps小鼠),测定B(1·61,3·23,6·46 mg·kg^(-1)·d^(-1),ip,8 d)和BL(以B计,1．61和3．23 mg·kg^(-1)·d^(-1),ip,8 d)对实体瘤小鼠的抑瘤率和腹水瘤小鼠的生命延长率;并比较各组实体瘤小鼠的体重、免疫器官(脾和胸腺)指数、血细胞指数(白细胞、红细胞、血小板和血红蛋白)和肝、肾功能指数(AST,ALT和BUN)。结果:低、中、高剂量的B(1．61,3．23,6．46 mg·kg^(-1)·d^(-1))对Heps实体瘤小鼠的抑瘤率分别为35．05%,43．70%,46．09%;同剂量的BL(1．61,3．23 mg·kg^(-1)·d^(-1))的抑瘤率分别为45．41%和58．19%。BL对Heps实体瘤小鼠的肿瘤抑制作用显著强于B,但B和BL对Heps腹水瘤小鼠生存时间均无延长作用。B和BL在1．61,3．23 mg·kg^(-1)·d^(-1)时对Heps实体瘤小鼠的造血、免疫系统以及肝、肾功能不仅无明显的毒性,相反还能提高其免疫器官的重量和指数,显著提高Heps小鼠的白细胞和血小板计数,并能显著降低Heps小鼠的AST,ALT和BUN的异常升高。结论:BL对移植性肝癌Heps小鼠的抗肿瘤活性明显强于B,并且对Heps小鼠造血、免疫系统以及肝肾的毒性低,通过深入研究BL可望成为一种新型的抗癌药物。Objective： To evaluate the effects and toxicity of brucine （B） versus brucine liposome （BL） against transplant tumor growth. Methods： ICR male mice （18-22 g） were inoculated hepatocarcinoma Heps cells. The Heps mice were randomly administered with B （1.61, 3.23 or 6. 46 mg· kg^-l·d^-l, ip） or BL （1.61 or 3.23 mg·kg^-1·d^-l in B weight, ip） for 8 days. The effectiveness was assessed based on tumor inhibitory ratio and survive time of mice with transplant Heps tumors. The toxicity was evaluated by measurements of the mice weight, immune organ weight, blood cell index （leuko- cyte, erythrocyte, platelet, and hemachrome protein, and hepatic function index （ALT and AST） and renal function index （BUN） of the Heps mice. Results： The B and BL showed an inhibition rate of 35.05% （1.61 mg·kg^-1·d^-1）, 43.70% （3.23 mg·kg^-1·d^-1） and 46.09% （6.46 mg·kg^-1·d^-1）versus 45.41% （ 1.61 mg· kg^-1· d^- 1） and 58.19% （ 3.23 mg·kg^-1·d^-1） , respectively, against Heps tumor growth. B and BL were found no significant difference in the prolongation of the life of Heps mice. B and BL enhanced the mice weight and immune organ index and improve the blood cell index and hepatic/renal function index. Conclusion： The brucine liposome was more superior and less toxic to bucine in the inhibition of tumor growth in Heps mice, suggesting that it is worthy to have a further investigation to confirm its anticancer activities.

关 键 词：马钱子碱 移植性肿瘤 Heps小鼠 抗肿瘤活性 毒性 

分 类 号：R285.5[医药卫生—中药学] R289.5[医药卫生—中医学]