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

摘要:

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。

Abstract:

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.