中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2009年
6期
443-449
,共7页
多廿醇%高脂血症%胆固醇%受体%LDL
多廿醇%高脂血癥%膽固醇%受體%LDL
다입순%고지혈증%담고순%수체%LDL
policosanol%hyperlipidemias%cholesterol%receptors,LDL
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4 mg·kg~(-1)预防组、高脂模型组、多廿醇4,6和8 mg·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8 mg·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.
目的 觀察多廿醇對高脂血癥大鼠的降膽固醇作用併探討其作用機製.方法 大鼠分為正常對照組、多廿醇4 mg·kg~(-1)預防組、高脂模型組、多廿醇4,6和8 mg·kg~(-1)治療組和洛伐他汀暘性對照組;後5組大鼠在實驗前4週給予高脂飼料製備高脂大鼠模型,從第5週開始,除正常對照和高脂模型組外,各給藥組ig給予不同濃度的多廿醇或洛伐他汀,每天1次,連續6週.多廿醇預防組餵飼高脂飼料的同時ig多廿醇,每天1次,連續10週.用全自動生化分析儀測定血清總膽固醇(TC)、甘油三酯(TG)、低密度脂蛋白膽固醇(LDL-C)和高密度脂蛋白膽固醇(HDL-C)水平,併測定糞便總膽汁痠(FBA)排齣量,紫外分光速率法測定肝髒微粒體3-羥基-3-甲基戊二痠單酰輔酶A(HMG-CoA)還原酶活性,熒光配體標記法測定外週血淋巴細胞低密度脂蛋白受體(LDL-R)活性.結果 與高脂模型組比較, 多廿醇預防組、多廿醇治療組和洛伐他汀暘性對照組大鼠血清TC含量明顯下降(39.1%～46.4%),LDL-C含量明顯下降(66.6%～80.7%), 糞便FBA明顯升高(9.7%～19.0%), 肝髒微粒體HMG-CoA還原酶活性明顯下降(13.8%～23.6%), 外週血淋巴細胞LDL-R活性升高(27.5%～129.6%);多廿醇預防組、多廿醇8 mg·kg~(-1)組和洛伐他汀組HDL-C水平明顯升高(12.2%～16.7%);洛伐他汀組TG水平明顯下降.結論 多廿醇具有明顯降低膽固醇的作用,其機製包括增加膽汁痠的排洩、抑製膽固醇閤成限速酶HMG-CoA還原酶活性和促進低密度脂蛋白受體活性的錶達.
목적 관찰다입순대고지혈증대서적강담고순작용병탐토기작용궤제.방법 대서분위정상대조조、다입순4 mg·kg~(-1)예방조、고지모형조、다입순4,6화8 mg·kg~(-1)치료조화락벌타정양성대조조;후5조대서재실험전4주급여고지사료제비고지대서모형,종제5주개시,제정상대조화고지모형조외,각급약조ig급여불동농도적다입순혹락벌타정,매천1차,련속6주.다입순예방조위사고지사료적동시ig다입순,매천1차,련속10주.용전자동생화분석의측정혈청총담고순(TC)、감유삼지(TG)、저밀도지단백담고순(LDL-C)화고밀도지단백담고순(HDL-C)수평,병측정분편총담즙산(FBA)배출량,자외분광속솔법측정간장미립체3-간기-3-갑기무이산단선보매A(HMG-CoA)환원매활성,형광배체표기법측정외주혈림파세포저밀도지단백수체(LDL-R)활성.결과 여고지모형조비교, 다입순예방조、다입순치료조화락벌타정양성대조조대서혈청TC함량명현하강(39.1%～46.4%),LDL-C함량명현하강(66.6%～80.7%), 분편FBA명현승고(9.7%～19.0%), 간장미립체HMG-CoA환원매활성명현하강(13.8%～23.6%), 외주혈림파세포LDL-R활성승고(27.5%～129.6%);다입순예방조、다입순8 mg·kg~(-1)조화락벌타정조HDL-C수평명현승고(12.2%～16.7%);락벌타정조TG수평명현하강.결론 다입순구유명현강저담고순적작용,기궤제포괄증가담즙산적배설、억제담고순합성한속매HMG-CoA환원매활성화촉진저밀도지단백수체활성적표체.
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.
