金黄地鼠高脂血症模型胆固醇代谢紊乱的生物标志物的研究  

Biomarkers of hyperlipidemia cholesterol metabolism in hamster

作　　者：康卓颖 初欣欣 杨润梅[1] 冀敏[1] 于莹[1,2] 高南南[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 [2]哈尔滨商业大学生命科学与环境科学研究中心,黑龙江哈尔滨150076

出　　处：《中国药理学通报》2014年第6期880-883,共4页Chinese Pharmacological Bulletin

基　　金：国家科技部"重大新药创制"专项-创新药物研究开发技术平台建设(No 2012ZX09301002-001-026)

摘　　要：目的建立金黄地鼠高脂血症模型,并对胆固醇代谢紊乱的分子机制进行探讨。方法金黄地鼠随机分为正常和模型组,正常组饲常规饲料,模型组饲高脂饲料,连续诱导4周。酶法检测血脂水平和CYP7A1活性,荧光实时定量PCR技术探讨金黄地鼠高脂血症模型胆固醇代谢紊乱的分子机制。结果金黄地鼠经高脂饲料诱导后与对照组比较,血清TC、LDL-C和TG明显升高,肝脏TC、TG明显增加。机制研究表明,模型组CYP7A1活性明显降低,肝脏LDL-R、SREBP-2、CYP7A1和LXRα表达下调,肝脏FXR表达上调。结论金黄地鼠经高脂饲料诱导后可形成以TC、LDL-C、TG升高为特征的高脂血症模型,LDL-R、SREBP-2、CYP7A1、FXR和LXRα既是金黄地鼠高脂血症模型胆固醇代谢紊乱的生物标志物,也是抗高胆固醇血症药物的作用靶标。Aim To establish the hyperlipidemic model and ex-plore the mechanism of hypercholesterolemia in hamster. Meth-ods Hamsters were randomly divided into the control and model groups. The hamsters in the control group were fed with the standard chow and the model group were fed with the high fat diet. Serum lipids and CYP7A1 activity were detected by enzymatic method. The molecular mechanism of cholesterol metabolism was investigated by real-time PCR. Results In comparison with the control group, the concentrations of serum TC, LDL-C, TG and hepatic TC, TG were significantly increased in the model group. The mechanism research showed that in hamsters fed with the high fat diet, the CYP7A1 activity and the mRNA expres-sions of hepatic LDL-R, SREBP-2, CYP7A1, LXRαwere down-regulated, the expression of hepatic FXR was up-regulated. Conclusion The hyperlipidemic model could be developed in hamsters fed with the high fat diet for 4 weeks. LDL-R, SREBP-2, CYP7A1, FXR and LXRαare the biomarkers of hypercholes-terolemia, and also the targets of hypolipidemic drugs.

关 键 词：金黄地鼠 高脂血症 LDL-R SREBP-2 CYP7A1 FXR LXRα1 

分 类 号：R332[医药卫生—人体生理学] R322.47[医药卫生—基础医学]