高效快速降脂动物模型研究

发布时间：2019-01-07 18:25

【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。
[Abstract]:To study the feasibility of zebrafish as a lipid-lowering drug screening model and the effect of bBR on the high-fat zebrafish. Serum total cholesterol (TC) and total triglyceride (TG) of zebrafish in control group, high-cholesterol group, 0.01% simvastatin group, 0.1% BBR group and 0.2% BBR group were determined by feeding 3-month-old zebrafish 0, 2, 4, 8, 14, 20, 25 and 30 d with 4% cholesterol feed. The levels of low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) were detected by RT-PCR. The expression of HMGCR, LDLR and CYP7A1a mRNA in the liver was detected by RT-PCR, and the changes of the fat content in the liver were detected by oil-red O-staining. The results showed that the level of TC, TG and LDL-c in zebrafish in BBR group decreased significantly, and the expression of HMGCR mRNA in BBR group decreased, and the expression of LDLR and CYP7A1a mRNA increased. the fat content is reduced, and a high-fat zebrafish model can be established by feeding the zebrafish for 20 days by the 4% cholesterol feed, and the research result lays a foundation for the further screening of the lipid-lowering drugs.
【作者单位】：西南大学生命科学学院;西南大学药学院;重庆中药现代化生产力促进中心;重庆市药物过程与质量控制工程技术研究中心;
【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)
【分类号】：R-332;R285.5

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