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载脂蛋白E(apoE)和脂蛋白脂酶(LPL)双基因敲除小鼠(apoE^-/-/LPL^+/-)用于大豆异黄酮调血脂作用研究
引用本文:于学慧,郝国祥,胡培欣,范琳琳,刘超,张成梅,张世栋. 载脂蛋白E(apoE)和脂蛋白脂酶(LPL)双基因敲除小鼠(apoE^-/-/LPL^+/-)用于大豆异黄酮调血脂作用研究[J]. 实验动物与比较医学, 2009, 29(1): 12-16. DOI: 10.3969/j.issn.1004-8448.2009.01.003
作者姓名:于学慧  郝国祥  胡培欣  范琳琳  刘超  张成梅  张世栋
作者单位:1. 山东大学实验动物中心,新药评价中心,药学院比较医学教研室,济南,250012
2. 山东大学药学院,济南,250012
3. 山东吴泰实验动物繁育有限公司,济南,250023
摘    要:目的探讨大豆异黄酮提取物对高胆固醇合并高甘油三酯血症基因工程小鼠的调血脂作用。方法高脂饮食条件下,以C57BL/6成年小鼠10只(65,早5)为正常对照,载脂蛋白E和脂蛋白脂酶双基因缺陷(apoE^-/-/LPL^+/-)成年小鼠(ELK小鼠)40只(620,早20),随机分为4组:高脂模型组,每天200mg/kg大豆异黄酮提取物,每周阳性对照药0.5mg/kg尼尔雌醇和每天20mg/kg洛伐他汀灌胃组。连续灌胃给药4周,测定血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和血糖含量。结果与C57BL/6空白对照组相比,ELK高脂模型组小鼠的血清TC、TG和LDL—c含量均极显著增高(P〈0.01)。与高脂模型组相比,大豆异黄酮给药4周可显著降低ELK小鼠血清TG含量(P〈0.05),同时使血清HDL—c增加9.3%,而洛伐他汀和尼尔雌醇组分别降低了13.5%和8.7%;高脂诱导的ELK小鼠血清TC、LDL—c水平极度增高,大豆异黄酮、洛伐他汀和尼尔雌醇均不能显著降低TC、LDL-c含量(P〉0.05)。结论大豆异黄酮有明显调血脂作用。

关 键 词:大豆异黄酮  apoE基因  LPL基因  基因敲除  apoE和LPL双基因缺陷(apoE^-/-/LPL^+/-)小鼠  血脂

Research on Blood Lipid Regulating Effects of Soybean Isoflavones by Both apoE and LPL Gene Deficient (apoE-/-/LPL+/-) Mice
YU Xue-hui,HAO Guo-xiang,HU Pei-xin,FAN Lin-lin,LIU Chao,ZHANG Cheng-mei,ZHANG Shi-dong. Research on Blood Lipid Regulating Effects of Soybean Isoflavones by Both apoE and LPL Gene Deficient (apoE-/-/LPL+/-) Mice[J]. Laboratory Animal and Comparative Medicine, 2009, 29(1): 12-16. DOI: 10.3969/j.issn.1004-8448.2009.01.003
Authors:YU Xue-hui  HAO Guo-xiang  HU Pei-xin  FAN Lin-lin  LIU Chao  ZHANG Cheng-mei  ZHANG Shi-dong
Affiliation:YU Xue-hui, HAO Guo-xiang, HU Pei-xin, FAN Lin-lin, LIU Chao, ZHANG Cheng-mei, ZHANG Shi-dong (1. Shandong University Laboratory Animal Center, Center for New Drug Evaluation, Institute of Comparative Medicine, School of Pharmaceutical Sciences, Shandong University, Jinan 250012,China; 2. Shandong HAOTAI Laboratory Animal Breeding Co. Ltd, Jinan, 250023,China; 3. School of Pharmaceutical Sciences, Shandong University, Jinan 250012,China)
Abstract:Objective To investigate the lipid regulating effects of soybean isoflavone extracts on genetic engineering mice with both hypercholesterolemia and hypertriglyceridemia. Method Under the western-type food conditioning, 10 ( ♂ 5, ♀ 5) adult C57BL/6 mice were used as control, 40 adult mice with both aopE and LPL gene deficiency (apoE^-/-/LPL^+/-) were divided into four groups, i.e., the group of animal models of hyperlipidemia, three groups of intragastric administration respectively with dose of 200 mg·kg^-1·d^-1 of soybean isoflavone extracts, 0.5 mg·kg^-1 of nylestrodial per week and 20 mg·kg^-1·d^-1 of lovastatin. After four weeks consecutive administration, concentration of serum total cholesterol, triacylglycerol, HDL cholesterol, LDL cholesterol and glucose were determined. Result Compared with the control mice of C57BL/6, the diet induced models of hyperlipidemia had a remarkable increase in triglyceride, total and LDL cholesterol (P〈0.01). Compared with models of hyperlipidemia, administration of soybean isoflavones had a favorable reduction in triglyceride (P〈0.05) and a 9.3% increase in HDL cholesterol, while administration of nylestrodial and lovastatin had 13.5% and 8.7% reduction in HDL cholesterol respectively. Probably due to the greatly increased total and LDL cholesterol in apoE^-/-/LPL^+/- mice, there is no effects of soybean isoflavone, nylestrodial and lovastatin on both the variables. Conclusion Soybean isoflavones had evident favorable lipid regulating effects.
Keywords:Soybean isoflavones  apoE gene  LPL gene  Gene knockout  apoE and LPL gene deficient (apoE^-/-/LPL^+/-) mice  Blood lipid
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