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[高效快速液体减少动物模型]

[Efficient and rapid liquid reduction animal model].

作者信息

Han Bing, Kou Shu-ming, Chen Biao, Peng Yao-zong, Wang Yue, Han Yu-long, Ye Xiao-li, Li Xue-gang

出版信息

Zhongguo Zhong Yao Za Zhi. 2015 Nov;40(22):4446-51.

Abstract

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 (TC), low density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) in serum were measured; the expression of hepatic HMGCR, LDLR and CYP7A1a 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 20th 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 CYP7A1a 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.

摘要

探讨建立斑马鱼降脂药物筛选模型的可行性及小檗碱(BBR)对高脂血症斑马鱼的影响。将3月龄斑马鱼用4%胆固醇喂养0、2、4、8、14、20、25、30天,检测血清总胆固醇水平。斑马鱼随机分为四组:对照组、高胆固醇饮食组、0.01%辛伐他汀治疗组、0.1%小檗碱治疗组和0.2%小檗碱治疗组。检测血清总胆固醇(TC)、甘油三酯(TC)、低密度脂蛋白胆固醇(LDL-c)和高密度脂蛋白胆固醇(HDL-c)水平;通过实时PCR检测肝脏HMGCR、LDLR和CYP7A1a mRNA的表达。进行油红O染色观察肝脏脂肪含量变化。结果显示,4%胆固醇饮食组血清TC水平随时间显著高于正常对照组,并在第20天达到稳定水平。小檗碱组TC、TG和LDL-c水平、HMGCR mRNA表达及脂肪含量显著降低,LDLR和CYP7A1a mRNA升高。通过4%胆固醇喂养20天成功建立高脂血症斑马鱼模型。本研究结果为进一步筛选降脂药物奠定了基础。

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