阿霉素纳米脂质体的免疫毒性研究  

Immunotoxicity effect of doxorubicin-nanoliposomes

作　　者：何霞[1] 季军[1] 姬尚义[1] 令文萍[1] 

机构地区：[1]深圳市孙逸仙心血管医院,广东深圳518020

出　　处：《中国现代医学杂志》2011年第28期3466-3470,3474,共6页China Journal of Modern Medicine

基　　金：国家十一五863纳米计划项目(No:2007AA021809)

摘　　要：目的探讨阿霉素纳米脂质体对实验小鼠的免疫毒性作用。方法小鼠经腹腔注射阿霉素纳米脂质体(按阿霉素有效治疗量6 mg/kg给药),注射5个周期后取血做血常规测定白细胞含量,测定免疫器官脏体比,淋巴细胞转化实验测刺激指数,免疫组化法检测脾脏细胞凋亡,ELISA法测IL-2、IL-1及TNF-α细胞因子含量,抗体及补体活性,选择测定小鼠腹腔巨噬细胞吞噬功能,测定迟发性超敏反应,常规病理观察主要脏器改变。结果阿霉素纳米脂质体实验组白细胞和淋巴细胞数量、胸腺和脾脏指数、脾脏淋巴细胞刺激指数、血清IL-1、IL-2含量、抗体(IgG、IgA、IgM和IgE)活性、补体C3、C4活性、巨噬细胞吞噬功能及迟发性变态反应均降低,与对照组比较差异有统计学意义(P<0.01);实验组脾细胞Fas-L表达与对照组比较明显增强,细胞凋亡增加,差异具有统计学意义(P<0.01)。实验组胸腺及脾脏淋巴细胞均明显减少,对照组未见明显异常。而阿霉素纳米脂质体实验组TNF-α含量与对照组相比差异无统计学意义(P>0.05);结论阿霉素纳米脂质体对小鼠具有免疫毒性作用。【Objective】To elucidate the immunotoxcity effect of doxorubicin-nanoliposomes on mice.【Methods】Doxorubicin-nanoliposomes were given through peritoneal injection at the doses of 6mg/kg（effective therapeutic dose of doxorubicin） to mice for five periods.Content of leucocyte was assayed by blood routine.Stimulation index were measured by lymphocyte transformation experiment.The apoptosis of spleen cells were observed using the method of immunohistochemical staining.Blood content of IL-2,IL-1,TNF-α and activity of antibody and complement were assayed by ELISA.The change of main organs was observed using routine pathology.The index of spleen and thymus,phagocytosis ability of peritoneal macrophage and delayed hypersensitivity were measured.【Results】The quantity of blood leucocyte and lymphocyte,index of spleen and thymus,stimulation index of lymphocyte,blood content of IL-2,IL-1,activity of antibody（IgG,IgA,IgM,IgE） and complement（C3,C4）,phagocytosis ability of macrophage and delayed hypersensitivity decreased in the experimental group,compared to control group（P 0.01）.The expression of Fas-L in spleen cell strengthened and apoptosis increased in the experimental group,compared to control group（P 0.01）.The quantity of lymphocyte of spleen and thymus decreased obviously in the experimental group,while no change was found in the control group.There was no significant difference in TNF-α content between two groups（P 0.05）.【Conclusions】Doxorubicin-nanoliposomes have immunotoxcity effect on mice.

关 键 词：阿霉素纳米脂质体 小鼠 免疫毒性 

分 类 号：R-332[医药卫生]