目的:探讨NPC1L1及其胆固醇代谢相关基因在高脂饮食诱导肝脏脂肪性变中的可能作用.方法:实验大鼠分为普通饮食组及高脂饮食组,饲喂8周后取肝脏组织,酶法测定肝脏组织中总胆固醇(TC)、磷脂、高密度脂蛋白(HDL)、甘油三酯(TG)含量,RT-PCR检测肝脏组织中NPC1L1,SREBP-1c,FAS及ABCAl基因的表达变化,并在光镜及电镜下观察肝脏病理变化.结果:高脂饮食大鼠肝脏组织TC(67.6±3.1mg/g vs 31.8±2.6 mg/g,P<0.01),TG(29.1±2.3 mg/g vs 12.5±1.6 mg/g,P<0.01)及磷脂(23.8士2.6 mg/g vs 19.8 ±2.2 mg/g,P<0.05)均较正常饮食大鼠增加.高脂饮食喂养组大鼠肝脏组织中胆同醇代谢相关基因NPC1L1(3.91±0.26,P<0.01),SREBP21e(2.84±0.23,P<0.01)、FASmRNA(6.45 4-0.25,P<0.01)表达水平显著高于正常饮食组,而ABCA1 mRNA(0.56±0.18,P<0.05)表达较正常饮食组降低.结论:肝脏组织NPC1L1表达增加及脂肪代谢相关基因SREBP-1c,FAS,ABCA1的表达
Role of Niemann-Pick C1-Like 1 in hepatic steatosis induced by high cholesterol diet
AIM: To determine the role of Niemann-Pick C1-Iike 1(NPC1L1) and other genes correlated with cholesterol metabolism in hepatic steatosis induced by high cholesterol diet. METHODS: After being fed with high cholesterol diet for 8 weeks, rats were anaesthetized, livers were weighed and hepatic TC, TC, HDL and phospholipid were extracted and measured by enzymatic methods. Hepatic sterol regulatory element binding protein-lc(SREBP-lc) , fatty acid synthase ( FAS ) , ATP binding cassette transporter A1 (ABCA1) and Niemann-Pick Cl-Like 1 (NPC1L1) mRNA levels were analyzed by real-time quantitative PCR. Pathological changes were observed by light microscope and electron microscope. RESULTS: Hepatic TC (67.6 ±3.1 mg/g vs 31.8±2.6 mg/g,P<0.01), TG (29. 1 ±2.3 mg/g vs 12.5 ±1.6 mg/g,P< 0.01) and phospholipid (23. 8 ±2. 6 mg/g vs 19.8 ±2. 2 mg/g,P < 0. 05 ) in high cholesterol group markedly increased compared with that in normal cholesterol group. Relative expression of NPC1L1 (3. 91 ± 0. 26, P < 0. 01 ) , SREBP-lc(2.84±0.23, P<0.01),FAS mRNA ( 6.45 ±0. 25, P < 0. 01 ) in high cholesterol group significant enhanced and ABCA1 mRNA(0. 56 ± 0. 18, P < 0. 05 ) decreased compared with that in normal cholesterol group. CONCLUSION: Enhanceof NPC1L1 and disturbance of SREBP-lc, AS, BCA1 might be involved in hepatic steatosis induced by high cholesterol diet.
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NSTL
万方数据
维普
