摘要
目的观察多廿醇对高脂血症大鼠的降胆固醇作用并探讨其作用机制。方法大鼠分为正常对照组、多廿醇4mg.kg-1预防组、高脂模型组、多廿醇4,6和8mg.kg-1治疗组和洛伐他汀阳性对照组;后5组大鼠在实验前4周给予高脂饲料制备高脂大鼠模型,从第5周开始,除正常对照和高脂模型组外,各给药组ig给予不同浓度的多廿醇或洛伐他汀,每天1次,连续6周。多廿醇预防组喂饲高脂饲料的同时ig多廿醇,每天1次,连续10周。用全自动生化分析仪测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,并测定粪便总胆汁酸(FBA)排出量,紫外分光速率法测定肝脏微粒体3-羟基-3-甲基戊二酸单酰辅酶A(HMG-CoA)还原酶活性,荧光配体标记法测定外周血淋巴细胞低密度脂蛋白受体(LDL-R)活性。结果与高脂模型组比较,多廿醇预防组、多廿醇治疗组和洛伐他汀阳性对照组大鼠血清TC含量明显下降(39.1%～46.4%),LDL-C含量明显下降(66.6%～80.7%),粪便FBA明显升高(9.7%～19.0%),肝脏微粒体HMG-CoA还原酶活性明显下降(13.8%～23.6%),外周血淋巴细胞LDL-R活性升高(27.5%～129.6%);多廿醇预防组、多廿醇8mg.kg-1组和洛伐他汀组HDL-C水平明显升高(12.2%～16.7%);洛伐他汀组TG水平明显下降。结论多廿醇具有明显降低胆固醇的作用,其机制包括增加胆汁酸的排泄、抑制胆固醇合成限速酶HMG-CoA还原酶活性和促进低密度脂蛋白受体活性的表达。
AIM To explore effects of policosanol on depressing cholesterol in hyperlipidemia rats and the correlated biochemistry mechanism.METHODS The rats were randomly divided into normal control,policosanol 4 mg·kg-1 prevention,hyperlipidemia model,policosanol 4,6 and 8 mg·kg-1 and lovastatin positive control groups.The later 5 group rats were fed with high-cholesterol diets for 4 weeks in order to make hyperlipidemia model and beginning from the 5th week,in addition to the normal control and model groups,other groups were ig given policosanol or lovastatin once a day for 6 weeks,respectively,and policosanol protection group rats were ig given with policosanol 4 mg·kg-1 once a day for 10 weeks,together with high-cholesterol diets everyday.Total cholesterol（TC）,triglycerides（TG）,low density lipoprotein cholesterol（LDL-C） and high density lipoprotein cholesterol（HDL-C） concentrations in the serum and fecal bile acid（FBA） in the exrement were determined by auto-biochemistry analyzer.The activity of 3-hydroxy-3-methyl-glutaryl coenzyme A（HMG-CoA） reductase in hepatocellular microsomes was detected by ultraviolet spectrophotometric analysis and activity of low density lipoprotein receptor（LDL-R） in peripheral blood lymphocyte was detected by fluorescence labelled integrator method.RESULTS Compared with hyperlipemia model group,the levels of TC decreased（39.1%-46.4%）,LDL-C decreased（66.6%-80.7%）,and FBA increased（9.7%-19.0%）,the activity of HMG-CoA reductase decreased（13.8%-23.6%）,and activity of LDL-R increased（27.5%-129.6%） in policosanol prevention,policosanol 4,6 and 8 mg·kg-1 and lovastatin groups,respectively;HDL-C increased（12.2%-16.7%） in policosanol prevention and policosanol 8 mg·kg-1 groups;TG decreased in lovastatin group.CONCLUSION Policosanol has significant effects on decreasing cholesterol.The decreasing cholesterol mechanism should include：① increasing FBA excretion;② decreasing the activity of HMG-CoA reductase;③ increasing activity of LDL-R.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2009年第6期443-449,共7页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金资助项目(30360091)~~
关键词
多廿醇
高脂血症
胆固醇
受体
LDL
policosanol
hyperlipidemias
cholesterol
receptors
LDL
