豚鼠高脂血症模型LDL-C代谢紊乱的机制研究  

Mechanism of hyperlipidemic LDL-C metabolic disorder in the guinea pig

作　　者：宋鑫[1] 高南南[1] 杨润梅[1] 刘芳[1] 

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所药理毒理研究中心,北京100193

出　　处：《中国药理学通报》2012年第3期342-346,共5页Chinese Pharmacological Bulletin

基　　金：北京市自然科学基金面上项目(No 7122112)

摘　　要：目的建立豚鼠高胆固醇血症模型,并对形成机制进行探讨。方法高脂饲料诱导法建立豚鼠高胆固醇血症模型,分别于造模1、2、4周检测血清脂质的动态变化;检测肝脏脂质;酶联免疫分析法测定血清ox-LDL浓度;实时荧光定量PCR法检测肝脏CYP7A1(cholesterol 7a-hydroxylaseA1)、肝脏法尼酯X受体(hepatic farnesoid X receptor,FXR)、肝X受体α(liver X receptor,LXRα)、HMG-CoA还原酶mRNA的相对表达;Western blot法检测肝脏LDL-R的蛋白表达情况。结果豚鼠经高脂饲料诱导1周后,模型组与对照组比较血清TC、LDL-C即发生升高,随造模时间延长,血脂一直维持在较高水平。造模4周后模型组血清ox-LDL、sd-LDL浓度,肝脏TC水平比正常组升高。肝脏HMG-CoA还原酶表达下调,LDL-R蛋白表达量明显高于正常组。值得注意的是豚鼠肝脏法尼酯X受体(FXR)表达明显上调,且肝X受体α(LXRα)表达也明显上调,但二者激活水平相当,最终未改变肝脏CYP7A1mRNA的表达水平。结论高脂诱导豚鼠形成高胆固醇血症主要与外源性胆固醇和低密度脂蛋白的清除发生障碍有关。Aim To establish the hyperlipidemic guinea pig model and investigate the mechanism of development.Methods Experimental hyperlipidemic guinea pig model induced by high-cholesterol diets was established.Serum lipids were determined after modeling 1,2 and 4 weeks,and the concentration of ox-LDL was also determined by ELISA.Real-time polymerase chain reaction to measure the expressions of CYP7A1,FXR,LXRα and HMG-CoA reductase mRNA.LDL-R was measured by western blot.Results In comparison with control group,serum TC and LDL-C were significantly increased after fed with high cholesterol diet for 1 week,and as time went by,the serum lipids remained at a high level.The concentrations of serum ox-LDL and sd-LDL were also increased.The model group had a greater accumulation of total cholesterol in the liver compared with the control group.The expression of CYP7A1mRNA had no change.The expression of HMG-CoA reductase mRNA occurred up-regulation.The mRNA levels of both hepatic farnesoid X receptor（FXR） and liver X receptor（LXR） were increased in the high-cholesterol group.Surprisingly,these receptors were activated,but the cholesterol did not affect CYP7A1 transcript levels.The protein expression of LDL-R in model group was obviously higher than the control group.Conclusions The development of guinea pig hyperlipidemic model induced by high fat diets is related to the elimination disorder of the exogenous high cholesterol and LDL-C.

关 键 词：豚鼠 高胆固醇血症 OX-LDL sd-LDL CYP7A1 FXR LXRΑ LDL-R 

分 类 号：R-332[医药卫生] R341.35