高效快速降脂动物模型研究  

Efficient and rapid liquid reduction animal model

作　　者：韩冰[1] 寇淑鸣 陈彪[1] 彭耀宗 王越[1] 韩玉龙[1] 叶小利[1,3,4] 李学刚[2,3,4] 

机构地区：[1]西南大学生命科学学院,重庆400715 [2]西南大学药学院,重庆400715 [3]重庆中药现代化生产力促进中心,重庆400715 [4]重庆市药物过程与质量控制工程技术研究中心,重庆400715

出　　处：《中国中药杂志》2015年第22期4446-4451,共6页China Journal of Chinese Materia Medica

基　　金：国家科技支撑计划项目(2011BAI13B02-1);高等学校博士学科点专项科研基金项目(20130182110023);重庆市百名高端工程技术人才计划项目(2013-2016)

摘　　要：探讨斑马鱼作为降脂药物筛选模型的可行性以及盐酸小檗碱(BBR)对高脂斑马鱼的影响。用含4%胆固醇饲料喂养3月龄斑马鱼0,2,4,8,14,20,25,30 d,检测血清总胆固醇含量的变化;测定对照组、高胆固醇组、0.01%辛伐他汀组、0.1%BBR组和0.2%BBR组斑马鱼血清总胆固醇(TC)、总甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)和高密度脂蛋白胆固醇(HDL-c)的水平;RT-PCR检测肝脏HMGCR,LDLR和CYP7A1a mRNA的表达水平;油红O染色检测肝脏中脂肪含量的变化。结果显示4%胆固醇喂养斑马鱼后血清TC水平升高且有时间依赖性,20 d基本达到稳定水平;BBR组斑马鱼血清TC,TG和LDL-c水平显著下降,肝脏HMGCR mRNA的表达下降,LDLR和CYP7A1a mRNA的表达升高,脂肪含量减少。4%胆固醇饲料喂养斑马鱼20 d即可建立高脂斑马鱼模型,研究结果为进一步开展降脂药物的筛选奠定基础。To investigate the practicability of establishing zebrafish lipid-lowering drug screening model and the effect of berberine（ BBR） on hyperlipidemic zebrafish. Three-month-old zebrafishes were fed with 4% cholesterol for 0,2,4,8,14,20,25,30 days,and the level of total cholesterol in serum was measured. Zebrafish were randomly divided into four groups： the control group,the high cholesterol diet group,the 0. 01% simvastatin-treated group,the 0. 1% berberine-treated group and the 0. 2% berberine-treated group.The levels of total cholesterol（ TC）,triglyceride（ TG）,low density lipoprotein cholesterol（ LDL-c） and high-density lipoprotein cholesterol（ HDL-c） in serum were measured; the expression of hepatic HMGCR,LDLR and CYP7A1 a mRNA expressions were detected by real time PCR. Oil red O staining was performed to observe the changes in fat content in the liver. According to the result,the level of serum TC in the 4% cholesterol diet group significantly was higher than that of the normal control group in a time-dependent manner and reached a stable level at the 20 th day. The BBR group showed significant decreases in the levels of TC,TG and LDL-c,HMGCR mRNA expression and fat content and increases in LDLR and CYP7A1 a mRNA. The hyperlipidemia zebrafish model was successfully established by feeding with 4% cholesterol for 20 days. The findings lay a foundation for further screenings on lipid-lowering drugs.

关 键 词：斑马鱼 高脂血症 盐酸小檗碱 HMGCR LDLR CYP7A1a 

分 类 号：R-332[医药卫生] R285.5