title: [A dyslipidemia animal model induced by poloxamer 407 in golden hamsters and pilot study on the mechanism].
abstract: The aim of this study is to establish a simple and stable model like poloxamer 407 (P-407)-induced dyslipidemia of golden hamster model, and investigate the mechanism of lipid metabolism disturbance in this model. PPARalpha agonist and HMG-CoA reductase inhibitor were administrated to validate the efficacy on regulating lipid metabolism in the dyslipidemia golden hamster model. Six weeks male golden hamsters were chosen to inject P-407 intraperitoneally at a bolus dose of 300 mg x kg(-1), an intermittent injection at a dose of 200 mg x kg(-1) every 72 hours after the bolus. The results showed that P-407-induced golden hamster model characterized as increased serum triglyceride (TG), total cholesterol (TC), free cholesterol (free-CHO), cholesteryl ester (CE), free fatty acids (FFA) and apoB levels, and the hyperlipidemia state maintained at a stable level persistently. Meanwhile, augmented malondialdehyde (MDA) and nitric oxide (NO) level was observed. LCAT and SR-B I mRNA levels in liver of model group were down-regulated (expression ratio is 0.426; 0.783), while HMG-CoA reductase mRNA level was up-regulated (expression ratio is 1.493) compared with those of the normal group. The serum cholesterol and triglyceride levels were significantly lower in P-407-induced dyslipidemia hamster model after treated with atorvastatin (Ato) at a dose of 50 mg x kg(1) or fenofibrate (Fen) at 100 mg x kg(-1) for two weeks. These findings suggest that serum lipid distribution in dyslipidemia golden hamster is similar to that of human, and which may be relevant to the disturbance of the enzymes expression involved in lipid metabolism in liver. Results obtained from this study support the concept that dyslipidemia golden hamster may be an adequate animal model to evaluate the efficacy of lipid-lowering agents.
authors.affiliation: Institute ofMateria Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education of PRC, Beijing 100050, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Shuai-nan
authors.initials: SN
authors.lastname: Liu
authors.forename: Lin-yi
authors.initials: LY
authors.lastname: Li
authors.forename: Zhi-yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Zhu-fang
authors.initials: ZF
authors.lastname: Shen
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000139:chemically induced / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008647:Mesocricetus; D009569:Nitric Oxide / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D020442:Poloxamer; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011758:Pyrroles; D012333:RNA, Messenger; D020442:Poloxamer; D009569:Nitric Oxide; D008315:Malondialdehyde; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D013482:Superoxide Dismutase; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011345:Fenofibrate