CAJ | 학술논문

目的：建立金黄地鼠高脂血症模型，并研究甘油三酯代谢紊乱的分子机制。方法金黄地鼠随机分为正常组和模型组，正常组饲常规饲料，模型组饲高脂饲料，连续诱导4周。于第2、4周检测血清TG、TC、LDL-C、FFA 水平和 LPL活性，应用荧光实时定量PCR技术探讨甘油三酯代谢紊乱的分子机制。同时观察阳性药非诺贝特对金黄地鼠高脂血症模型血脂的影响。结果金黄地鼠造模2周时，血清TG、TC、LDL-C、FFA与对照组比较分别升高2.57、1.93、2.49和1.25倍；造模4周时分别升高3.93、1.90、2.27和2.29倍。阳性药对TG和FFA升高有明显的抑制作用。机制研究表明，金黄地鼠造模后，肝脏AMPK、PPARα、CPT-1 mRNA表达降低，SREBP-1 c、ACC、SCD-1、AGPAT2、DGAT2 mRNA 表达上调。ApoB表达有上调趋势，MTTP和 LPL 表达有下调趋势，血浆LPL活性明显降低。这些酶、蛋白、受体的表达变化是金黄地鼠甘油三酯代谢紊乱的主要原因。结论金黄地鼠经高脂饲料诱导4周后形成了具有高甘油三酯血症特征的高脂血症模型，AMPK、SREBP-1 c、ACC、SCD1、DGAT2、AG-PAT2、PPARα、CPT-1、LPL既是金黄地鼠甘油三酯代谢紊乱的生物标志物，也是降甘油三酯药物的作用靶标。
목적：건립금황지서고지혈증모형，병연구감유삼지대사문란적분자궤제。방법금황지서수궤분위정상조화모형조，정상조사상규사료，모형조사고지사료，련속유도4주。우제2、4주검측혈청TG、TC、LDL-C、FFA 수평화 LPL활성，응용형광실시정량PCR기술탐토감유삼지대사문란적분자궤제。동시관찰양성약비낙패특대금황지서고지혈증모형혈지적영향。결과금황지서조모2주시，혈청TG、TC、LDL-C、FFA여대조조비교분별승고2.57、1.93、2.49화1.25배；조모4주시분별승고3.93、1.90、2.27화2.29배。양성약대TG화FFA승고유명현적억제작용。궤제연구표명，금황지서조모후，간장AMPK、PPARα、CPT-1 mRNA표체강저，SREBP-1 c、ACC、SCD-1、AGPAT2、DGAT2 mRNA 표체상조。ApoB표체유상조추세，MTTP화 LPL 표체유하조추세，혈장LPL활성명현강저。저사매、단백、수체적표체변화시금황지서감유삼지대사문란적주요원인。결론금황지서경고지사료유도4주후형성료구유고감유삼지혈증특정적고지혈증모형，AMPK、SREBP-1 c、ACC、SCD1、DGAT2、AG-PAT2、PPARα、CPT-1、LPL기시금황지서감유삼지대사문란적생물표지물，야시강감유삼지약물적작용파표。
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.