橙皮苷对辛伐他汀调脂作用及细胞色素P4503A mRNA表达的影响

Influences of hesperidin on the regulation of serum lipids levels by simvastat in and CYP4503A mRNA expression

目的 研究橙皮苷对辛伐他汀 (simvastatingroup ,SV)调脂作用及CYP450 3AmRNA表达的影响。方法 将Wistar大鼠随机分为 :对照组 (controlgroup)、高脂血症模型组 (modelgroup)、辛伐他汀组 (simvastatingroup ,SVgroup)、低剂量橙皮苷 +辛伐他汀组 (lowdosehesperidin +SV group ,LDHS)、高剂量橙皮苷 +辛伐他汀组 (highdosehesperidin +SV group ,HDHS)。除对照组外 ,余组均饲喂高脂饮食 ,各实验组按 5mg·kg- 1SV灌胃 ,并分别加用不同剂量的橙皮苷。实验 8wk后 ,检测各组大鼠血脂水平 ,肝脏及小肠CYP450 3A基因表达水平。结果 高脂饲养 8wk后 ,模型组TC、TG和LDL C均升高 (P <0 0 1) ;SV组TC、TG和LDL C较模型组降低 (P <0 0 1或P <0 0 5) ;加用橙皮苷后 ,TC和TG均较SV组呈剂量依赖性降低。模型组肝脏CYP450 3AmRNA表达量与对照组比较无统计学意义 (P >0 0 5) ,小肠CYP450 3AmRNA表达量较对照组升高 (P <0 0 5)。使用SV后 ,肝脏CYP450 3AmRNA表达量较模型组有增加趋势 ,小肠表达量增加 (P <0 0 5)。SV与橙皮苷合用后 ,随橙皮苷剂量的加大 ,肝脏及小肠CYP450 3AmR NA的表达呈下降趋势 ,以HDHS组明显 (P <0 0 5)。结论 橙皮苷能增加SV的调脂作用 ,其机制可能与橙皮苷抑制了CYP450 3A基因表达?

AIMTo study the influences of hesperidin on the regula tion of serum lipids levels by simvastatin and its mechanism. METHODS Wistar rats were divided randomly into five groups:control group,model g roup,simvastatin group(SV group), low dose hesperidin +SV group(LDHS group) and high dose hesperidin+SV group(HDHS group).The control group were fed with common diet. The model group were fed with high lipid diet. Other groups were fed with diet containing high lipid,5 mg·kg -1 SV and different doses of hesperid in accordingly. After 8 experimental weeks,the serum lipids levels and CYP4503Am RNA expression in livers and small bowels of the rats were detected. RE SULTSAfter 8 weeks of high lipid diet, the levels of TC,TG and LDL-C in model groups increased significantly (P<0 01).The levels of TC,TG and LDL -C in simvastatin groups decreased significantly versus model groups(P<0 01 or P<0 05). The levels of TC,TG and LDL-C in groups fed with hesperidi n decreased in a dose-dependent manner versus the groups fed with simvastatin a lone. The levels of CYP4503A mRNA expression had no significant changes in the l iver,but significantly increased in the small bowel of model groups v ersus control groups. The expressions were found to be higher in liver, and were sig nificantly higher in small bowel of simvastatin group than that of model groups. When hesperidin were added, the levels of CYP4503A mRNA in liver and small bowe l had a decreasing tendency and significantly decreased in HDHS group(P<0 05). CONCLUSIONHesperidin enhances the regulating effects of sim vastatin on serum lipids profile. The mechanisms might be related to its effect on suppressing CYP4503A mRNA expression in livers and small bowel.