Effects Of Simvastatin On Apolipoprotein M In Vivo And In Vitro

Objective To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells.Methods Fifty Kunming male mice at 12 weeks old were randomly divided into two groups, i.e., high fat group and control group. Mice were intragastrically fed 0.9% saline(Control group)or lipid emulsion (High fat group) at the daily dosage as 15ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were randomly divided into three experimental groups: vehicle control group, high-dose simvastatin–treated group (100 mg/kg body wt), and low-dose simvastatin–treated group (10 mg/kg body wt). Mice were dosed daily for 6 weeks of simvastatin before mice were sacrificed for the determination of serum lipid profile and apoM protein level that was determined by using dot blotting analysis. Effects of simvastatin on apoM mRNA expression in the HepG2 cells were determined by the real-time RT-PCR.Results Comparing to high fat model mice without simvastatin treatment, 100mg/kg simvastatin could significantly increase serum total cholesterol (P<0.05). In the present study, we demonstrated that serum apoM levels, in all mice, were significantly lower in the mice at the age of 26 weeks than in the mice at 12 weeks old (P<0.05), which indicated that serum apoM levels were significantly correlated to the mice age. It is also demonstrated that treatment of simvastatin did not influence serum apoM levels in these mice, although serum apoM levels were increased by 13.13% in the 10mg/kg simvastatin group than in the vehicle control group without simvastatin. In HepG2 cell cultures, it demonstrated that simvastatin could significantly decrease apoM mRNA levels, at 10μM simvastatin treatment, apoM mRNA decreased by 51.93% compared to the controls. It is also demonstrated that simvastatin induced inhibition of apoM expression if time dependent. Conclusion The present study suggested that simvastatin, in vivo, had no effect on apoM levels in the hyperlipidemic mouse model. ApoM serum levels in mice were significantly correlated to the animal's age. Whereas in cell cultures simvastatin does inhibit apoM expression in the HepG2 cells.