目的探讨红曲有效成分洛伐他汀对高脂小鼠血脂代谢调节的分子机制。方法昆明种雌性小鼠48只,按血清总胆固醇(TC)分为A、B、C、D、E、F 6组:正常对照组、高脂对照组、绞股蓝总苷阳性对照组、洛伐他汀低、中、高(5、15、30 mg/kg)剂量组。A组喂饲基础饲料,其他各组喂饲高脂饲料;按剂量分别ig给药6周,禁食12 h后,测定小鼠血脂水平相关指标;用Trizol试剂法提取总RNA,用反转录聚合酶链反应(RT-PCR)法检测肝、脾组织脂蛋白脂酶(LPL)mRNA的表达。结果实验6周末,洛伐他汀低、中、高各剂量组使小鼠动脉硬化指数(AI)均极显著低于高脂组(P<0.01);洛伐他汀中、高剂量组和绞股蓝总苷阳性对照组使高脂小鼠血清TC、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)均极显著低于高脂组(P<0.01);洛伐他汀低、中、高剂量组与高脂组相比,显著升高血清高密度脂蛋白-胆固醇(HDL-C)(P<0.01);洛伐他汀低、中、高剂量组均提高肝组织中LPLmRNA的表达,且呈剂量依赖关系。结论洛伐他汀通过促进LPL mRNA转录而调节高脂小鼠血清血脂代谢水平,这可能是其调节血脂,预防动脉粥样硬化(AS)等心脑血管疾病的机制之一。

Objective To study the effect of Lovastatin from Red Kojic on lipid metabolism in mice fedhigh-fat diet and its anti-hyperlipidemic molecular mechanism. Methods According to serum TC level, 48female mice were randomly divided into six groups: A-normal control group; B-high-fat control group; C-Gypenosides (20 mg/kg) positive control group; D, E, F-Lovastatin 5, 15, and 30 mg/kg groups. GroupA was fed basic diet and the other groups were fed high-fat diet for six weeks. Groups A and B were ignormal water, group C was ig Gypenosides 20 mg/kg, and groups D, E, F were ig Lovastatin 5, 15, and30 mg/kg, respectively. Blood lipid levels were determined after 12 h-starvation. The mRNA expressionof lipoprotein lipase (LPL) in liver and spleen was detected by reverse transcription polymerase chain reac-tion (RT-PCR). Results Serum TC, TG, and LDL-C level were significantly lower in groups C, E, Fthan in group B, group D was lower than group B, but there was not significantly different at the end ofsix weeks. Serum HDL-C levels were significantly higher in groups D, E, F than in group B. AI was sig-nificantly lower in groups D, E, F than in group B. Lovastatin increased the expression of LPL mRNA inliver dose-dependently. Conclusion It is suggested that Lovastatin could modulate blood lipid by promot-ing mRNA expression of LPL in liver. This may be one important mechnaism of Lovastatin to modulateblood lipid and prevent atherosclerosis (AS).

湖北省自然科学基金项目(2002AB080)