纳豆红曲复合物的降脂作用及药代动力学分析

Lipid-lowering Effect and Pharmacokinetic Analysis of Natto-monascus Complex

该研究旨在考察纳豆红曲复合物(NMC)的降脂作用,及其成分洛伐他汀的药物代谢动力学特征。SD大鼠分为正常组、模型组、NMC低、中、高剂量组和阳性药洛伐他汀组,除正常组外,其余各组大鼠采用高脂饮食诱导高脂血症模型。连续灌胃给药4周后检测各组大鼠血清中总胆固醇(TC)、总甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量,并对肝组织切片进行染色分析。该研究还采用LC-MS法检测比格犬灌胃NMC后血浆中洛伐他汀的含量变化。结果显示,低、中、高剂量给药均可显著降低(p<0.01)高脂饮食诱导大鼠的LDL-C和TG水平,高剂量给药还可显著降低(p<0.01)TC水平。中、高剂量给药还可改善高脂饮食诱导大鼠的肝脏细胞脂质蓄积程度。此外,NMC单次口服给药后,洛伐他汀在比格犬体内的达峰时间为1.17 h,最大血药浓度为62.33 mg/mL,消除半衰期为5.95 h,体内滞留时间为7.83 h。该研究证明NMC可降低高脂饮食诱导大鼠的血脂水平,并分析了洛伐他汀在比格犬体内的代谢动力学特征,结果可为纳豆、红曲类食品的研发提供依据。

The lipid-lowering effect of natto-monascus complex(NMC)and the pharmacokinetic characteristics of its component lovastatin was investigated.SD rats were divided into normal group,model group,NMC low-,medium-and high-dose groups,and positive drug lovastatin group.Except for the normal group,the rats in the other groups were fed a high-fat diet to induce hyperlipidemia.The contents of total cholesterol(TC),total triglycerides(TGs),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)in the sera of rats in each group were measured after 4 weeks of continuous intragastric administration,and the liver tissue sections were stained with hematoxylin-eosin for analysis.In this study,the changes in the content of lovastatin in plasma of beagle dogs after oral administration of NMC were measured by LC-MS.The results showed that the administration of low-,medium-and high-doses of NMC decreased significantly(p<0.01)the levels of LDL-C and TG in high fat diet-induced rats,and the level of TC decreased significantly(p<0.01)in the high-dose group.Moreover,medium-and high-doses of NMC could ameliorate lipid accumulation in the livers by high fat diet in rats.In addition,after a single oral administration of NMC,the time for lovastatin in beagle dogs to reach the peak amount was 1.17 h,with the maximum plasma concentration being 62.33 mg/mL,the elimination half-life being 5.95 h,and the retention time being 7.83 h.This study proves that NMC can reduce the level of blood lipids in rats induced by the high-fat diet,and provides apreliminary analysis of the pharmacokinetic characteristics of lovastatin in beagle dogs. The research results can provide abasis for the research and development of natto-monascus foods.