Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund, Sweden.
Lipids Health Dis. 2011 Jul 5;10:112. doi: 10.1186/1476-511X-10-112.
To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells.
Swiss male mice were randomly divided into the high fat group and control group, and were intragastrically fed with 0.9% saline (control group) or lipid emulsion (high fat group) at the daily dosage of 15 ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were then randomly divided into three experimental groups: vehicle control group, high-dose simvastatin-treated group (100 mg/kg body weight), and low-dose simvastatin-treated group (10 mg/kg body weight). Mice were dosed daily for 6 weeks of simvastatin before mice were sacrificed for determining serum lipid profile and apoM protein levels that was determined by using dot blotting analysis. Effects of simvastatin on apoM mRNA expression in the HepG2 cells were determined by real-time RT-PCR.
Comparing to high fat model mice without simvastatin treatment, 100 mg/kg simvastatin could significantly increase serum total cholesterol (P < 0.05). Serum apoM levels, in all mice, were significantly lower in the mice at the age of 26 weeks than the mice at 12 weeks old (P < 0.05), which indicated that serum apoM levels were significantly correlated to the mice age. It demonstrated also that treatment of simvastatin did not influence serum apoM levels in these mouse model, although serum apoM levels were increased by about 13% in the 10 mg/kg simvastatin group than in the vehicle control group without simvastatin. In HepG2 cell cultures, simvastatin could significantly decrease apoM mRNA levels with dose- and time-dependent manners. At 10 μM simvastatin treatment, apoM mRNA decreased by 52% compared to the controls.
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. The mechanism behind it is not known yet.
研究降脂药物辛伐他汀对高脂血症小鼠和 HepG2 细胞载脂蛋白 M 表达的影响。
雄性瑞士小鼠随机分为高脂组和对照组，分别给予 0.9%生理盐水（对照组）或脂质乳剂（高脂组）灌胃，每日 15ml/kg 体重。8 周后成功诱导高脂血症模型，然后将这些高脂血症小鼠随机分为三组：空白对照组、高剂量辛伐他汀组（100mg/kg 体重）和低剂量辛伐他汀组（10mg/kg 体重）。在处死小鼠之前，通过斑点印迹分析测定血清脂质谱和载脂蛋白 M 蛋白水平，小鼠每日给予辛伐他汀治疗 6 周。实时 RT-PCR 法测定辛伐他汀对 HepG2 细胞载脂蛋白 M mRNA 表达的影响。
与未用辛伐他汀治疗的高脂模型小鼠相比，100mg/kg 辛伐他汀可显著增加血清总胆固醇（P<0.05）。所有小鼠的血清 apoM 水平在 26 周龄时均显著低于 12 周龄时（P<0.05），表明血清 apoM 水平与小鼠年龄显著相关。这也表明，尽管 10mg/kg 辛伐他汀组的血清 apoM 水平比未用辛伐他汀的空白对照组增加了约 13%，但辛伐他汀治疗并没有影响这些小鼠模型中的血清 apoM 水平。在 HepG2 细胞培养中，辛伐他汀可显著降低 apoM mRNA 水平，呈剂量和时间依赖性。在 10μM 辛伐他汀处理时，apoM mRNA 与对照组相比降低了 52%。
本研究表明，辛伐他汀在体内对高脂血症小鼠模型中的 apoM 水平没有影响。小鼠的 apoM 血清水平与动物的年龄显著相关，而在细胞培养中，辛伐他汀可抑制 HepG2 细胞中 apoM 的表达。其机制尚不清楚。
