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.