泊洛沙姆诱导急性高脂血症小鼠模型的药效学研究  

Studies on the acute hyperlipidemia model induced by poloxamer 407 in mice

作　　者：霍志军[1] 柳莲[1] 赵珍[1] 吉蕊[1] 郭月芳[1] 王志勇[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室,上海200040

出　　处：《世界临床药物》2014年第5期305-309,共5页World Clinical Drug

摘　　要：目的通过泊洛沙姆诱导建立急性高脂血症小鼠模型。方法 ICR小鼠单次腹腔注射不同剂量的泊洛沙姆407(P-407)(用量依次为0.25 g/kg、0.50 g/kg、1.0 g/kg、2.0 g/kg),然后在指定的时间点(次)从眼窝丛收集血液样本,测定血清中TG、TC、AST、ALT、HDL、LDL及血糖水平并观察经阿托伐他汀预处理后的血脂水平。结果 P-407可诱发ICR小鼠血脂水平出现异常,其中0.25、0.50和1.0 g/kg剂量组小鼠ALT、AST以及血糖水平并无显著改变,但2.0 g/kg剂量组小鼠ALT水平显著升高;阿托伐他汀能有效改善0.25和0.50 g/kg剂量P-407诱发的血脂异常。结论 0.25和0.50 g/kg剂量的P-407可用于复制急性高脂血症小鼠模型,此模型可用于药物的筛选,其对血糖水平和肝功能不受影响。Objective To establish an acute hyperlipidemia model with poloxamer in mice. Methods Animal＇s hyperlipidemia was induced by poloxamer 407 through a single intraperitoneal injection. The blood samples at the indicated time point（s） following P-407 injection were collected from the retro-orbital plexus and centrifuged to gather the serum for biochemical analyses. Then the blood samples were withdraw from the eye vein and the TG、TC、AST、ALT、HDL、LDL and glucose in serum were measured. Results P-407 can induce abnormal changes of serum lipid levels at indicated doses with no alterations of blood glucose, ALT and AST in ICR mice. Particularly, the hyperlipidemic model by P-407 at the dose of 0.25 g/kg and 0.50 g/kg effectively refl ects the efficacy of the lipid-lowering agent atorvastatin. Conclusion An appropriate dose of P-407 can be used for acute hyperlipidemic model in ICR mice for drug screening with out alterations of blood glucose, ALT and AST.

关 键 词：脂质代谢 泊洛沙姆 高血脂小鼠 阿托伐他汀 

分 类 号：R965[医药卫生—药理学] R969[医药卫生—药学]