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单次灌胃给予五味子乙素/胆固醇/胆盐混合物建立的合并脂肪变性和肝损伤的新型高脂血症小鼠模型。

Novel mouse model of combined hyperlipidemia associated with steatosis and liver injury by a single-dose intragastric administration of schisandrin B/cholesterol/bile salts mixture.

机构信息

Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China.

出版信息

J Pharmacol Sci. 2013;123(2):110-9. doi: 10.1254/jphs.13087fp. Epub 2013 Oct 4.

DOI:10.1254/jphs.13087fp
PMID:24096833
Abstract

Hyperlipidemia is referred to as hypercholesterolemia, hypertriglyceridemia, or both in combined hyperlipidemia. Here, a novel mouse model of combined hyperlipidemia is described. Mice were orally given a single dose of a modeling agent (MA) made of a mixture of schisandrin B/cholesterol/bile salts (1/2/0.5 g/kg) suspended in olive oil. MA treatment increased serum triglycerides (TG) and total cholesterol (TC) (up to 422% and 100% at 12 - 96 h post-treatment, respectively) and hepatic TG and TC (up to 220% and 26%, respectively) in a time- and dose-dependent manner, associated with elevation of high-density lipoprotein and low-density lipoprotein levels. Serum alanine/aspartate aminotransferase activities, indicators of liver cell damage, were also elevated (up to 198%) at 48 and 72 h post-MA treatment. Fenofibrate blocks MA-induced hyperlipidemia, lipid accumulation in the liver, as well as liver injury. Oral administration of a mixture of schisandrin B, cholesterol, and bile salt could generate an interesting mouse model of combined hyperlipidemia associated with hepatic steatosis and steatohepatitis.

摘要

高脂血症是指高胆固醇血症、高三酰甘油血症或混合性高脂血症。这里描述了一种新型的混合性高脂血症小鼠模型。小鼠经口给予由五味子乙素/胆固醇/胆汁盐混合物(1/2/0.5 g/kg)悬浮于橄榄油中的单一剂量造模剂(MA)。MA 处理以时间和剂量依赖的方式增加血清三酰甘油(TG)和总胆固醇(TC)(处理后 12-96 小时分别高达 422%和 100%)和肝 TG 和 TC(分别高达 220%和 26%),同时升高高密度脂蛋白和低密度脂蛋白水平。血清丙氨酸/天冬氨酸转氨酶活性(肝损伤的指标)在 MA 处理后 48 和 72 小时也升高(高达 198%)。非诺贝特可阻断 MA 诱导的高脂血症、肝脏脂质蓄积以及肝损伤。五味子乙素、胆固醇和胆汁盐的混合物经口服给药可产生一种有趣的与肝脂肪变性和脂肪性肝炎相关的混合性高脂血症小鼠模型。

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