阳离子脂质体作为基因治疗药物载体在小鼠体内的毒性研究  

Toxicity of cationic liposomes as medicines carriers for gene therapy in mice

作　　者：邓益斌[1] 秦爱萍[2] 朱晓莹[1] 王燕菲[1] 

机构地区：[1]广州医学院生物化学与分子生物学教研室,广东广州510182 [2]广州医学院病理生理学教研室,广东广州510182

出　　处：《现代生物医学进展》2008年第12期2238-2241,共4页Progress in Modern Biomedicine

基　　金：广州市科技计划项目(编号2002Z3-E4081)

摘　　要：目的:探讨阳离子脂质体作为基因治疗药物载体在小鼠体内的毒性。方法:采用流体动力学法,经尾静脉给小鼠注射不同剂量的阳离子脂质体,对照组注射等量5%GLU液。于注射前、注射后第1天和第3天,经眶静脉采血,用自动血球计数仪测定外周抗凝血中的白细胞(WBC)、淋巴细胞(LY%)、中性粒细胞(GR%)。用自动生化分析仪测定血浆中的清蛋白(Alb)、谷丙转氨酶(ALT)、尿素氮(BUN)、肌酐(CR)。同时做脏器组织切片HE染色,观察肝、肾脏组织结构的变化。结果:与对照组比较,12μl/g剂量以上组的WBC、BUN、CR均明显升高(P<0.05),ALT、Alb无显著性差异(P>0.05)。12μl/g剂量以下组无明显变化(P均>0.05)。与注射前比较,注射后第1天,WBC、BUN、CR显著升高(P<0.05),而注射后第3天除CR外均基本恢复正常(P>0.05)。而ALT、Alb无显著性差异(P>0.05)。肝肾脏组织切片HE染色,各荆量组间组织结构变化无差异。结论:阳离子脂质体对小鼠外周血相和肾脏功能的毒性作用呈剂量和时间依赖性,故使用其作为核酸药物载体用于基因治疗研究时,剂量应小于12ul/g体重,给药时间应隔1天以上。Objective： To investigate the toxicity of cationic liposomes as medicines carriers for gene therapy in mice. Methods： The cationic liposomes with different dosage were injected into mice through tail vein by hydrokinetics method. For the control group, each mouse was injected with the same volume 5 % glucose solution in the same way.Venous blood samples were collected separately in the previous day, the 1st day and the 3rd day after the injection via orbital vein. WBC, Lycys % and neutrophil % in the anticoagnlated blood were detected by automatic globulimeter, while serum Alb, ALT,BUN and Crea were measured by automatic biochemistry analyzer.Three days later the mice were killed and HE staining was used to examine the liver and kidney. Pathological examination of the tissues was performed. Results： When compared with the control group, WBC, BUN and Crea were significantly higher in the 24 μl/g body weight group （P〈0.05）, and Alb, ALT didn＇t show any significant differences （P〉0.05）. No significant abnormality was found in I the other groups （P〉0.05）. When compared with previous injection group, WBC, BUN and Crea were significantly higher in 1 day after the injection（P〈0.05）, and all targets were returned to normal level except for Crea in 3 days after the injection（P〉0.05）. Alb, ALT didn＇t show any significant differences （P〉0.05）. No significant abnormality was found in the tissues in all groups. Conclusion： The toxicity of cationic liposomes in low volume （〈12 μl/g body weight） is slight, so the cationic liposomes can be used to carry nuclentide medicines for gene therapy.

关 键 词：脂质体 基因治疗 药物载体 毒性 

分 类 号：R961[医药卫生—药理学]