A 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

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  • Pan Si-Yuan
    Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
  • Jia Zhan-Hong
    Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
  • Zhang Yi
    Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
  • Yu Qing
    Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
  • Wang Xiao-Yan
    Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
  • Sun Nan
    Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
  • Zhu Pei-Li
    Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
  • Yu Zhi-Ling
    School of Chinese Medicine, Hong Kong Baptist University, China
  • Ko Kam-Ming
    Division of Life Science, Hong Kong University of Science & Technology, China

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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.

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