中国药理学通报Issue(7):1012-1017,6.DOI:10.3969/j.issn.1001-1978.2014.07.027
金黄地鼠高脂血症模型甘油三酯代谢紊乱的生物标志物的研究
Triglyceride disorder biomakers in hyperlipidemic hamsters
摘要
Abstract
Aim To establish hyperlipidemic model and study the molecular mechanism of triglyceride (TG)disorder in hamsters.Methods The male ham-sters were randomly divided to control group fed with standard diet and model group fed with high-fat diet, both of the groups had been fed with diet for 4 weeks. The levels of serum TG,TC,LDL-C,FFA were detec-ted at the end of 2nd and 4th week.The hepatic TG, TC,LPL activity were detected by enzymatic method at the end of 4th week.The molecular mechanism was tested by real-time PCR.Meanwhile the effect of posi-tive drug fenofibrate on the model of hyperlipidemia in hamsters was investigated.Results Compared with the control,the serum levels of TG,TC,LDL-C,FFA in the model group increased 2.57,1.93,2.49,1.25 times at the end of2nd week,and 3.93,1.90,2.27, 2.29 times at the end of 4th week,respectively.The positive drug significantly decreased the concentrations of serum TG and FFA. The mechanism research showed that the hepatic AMPK,PPARα,CPT-1 mRNA decreased in hamsters fed with high-fat diet,and the SREBP-1 c,ACC,SCD-1 ,AGPAT2,DGAT2 mRNA ex-pressions increased.The hepatic ApoB mRNA expres-sion was up-regulated while the MTTP and LPL mRNA expressions were down-regulated slightly.LPL activity significantly decreased in model hamsters compared with the control.The alternations of these enzymes and receptors were the critical factors for TG disorder. Conclusion The hamsters fed with high-fat diet for 4 weeks can form a good hyperlipemic model with HTG feature.AMPK,SREBP-1 c,ACC,SCD-1 ,DGAT2,AG-PAT2,PPARα,CPT-1 and LPL are not only the main mechanisms of TG disorder,but also the biomarkers of hypotriglyceridemic drugs.关键词
金黄地鼠/高脂血症/甘油三酯代谢紊乱/AMPK/SREBP-1 c/ACC/SCD-1/AGPAT2/DGAT2/PPARα/CPT-1/LPLKey words
hamsters/hyperlipemia/TG disorder/AMPK/SREBP-1 c/ACC/SCD-1/AGPAT2/DGAT2/PPARα/CPT-1/LPL分类
医药卫生引用本文复制引用
初欣欣,杨润梅,于莹,康卓颖,冀敏,高南南..金黄地鼠高脂血症模型甘油三酯代谢紊乱的生物标志物的研究[J].中国药理学通报,2014,(7):1012-1017,6.基金项目
国家科技部“重大新药创制”科技重大专项资助项目 ()