·糖尿病基础研究·

　　汤世国 李伶 杨刚毅 孙滨 李钶 晏丕军 李龙辉 董靖 吴丹冬

　　项目基金：国家自然科学基金项目(30771037, 30871199, 30971388)

　　作者单位：400010重庆医科大学附属第二医院内分泌科(汤世国、杨刚毅、李钶、晏丕军、李龙辉、董靖、吴丹冬);重庆医科大学检验系临床生化教研室和教育部实验诊断重点实验室(李伶、孙滨)

　　通讯作者：杨刚毅，E-mail：gangyiyang@yahoo.com.cn

　　【摘要】目的探讨高脂诱导IR apoE-/-小鼠胆固醇代谢基因的变化。方法健康雄性apoE-/-小鼠，随机分为普食组(NF组)和高脂喂养组(HF组)，共喂养16周。采用实时荧光定量PCR测定肝组织羟甲基戊二酸单酰辅酶A还原酶(HMGCR)、固醇调节元件结合蛋白-2(SREBP-2)、低密度脂蛋白受体(LDLr)基因mRNA表达。结果HF组小鼠FBG、FIns、TC、TG、HDL-C、LDL-C和FFA水平均明显升高(P均<0.01)。HF组小鼠肝脏HMGCR、SREBP-2和LDLr mRNA表达水平均明显降低(P<0.01或P<0.05)。结论在高脂喂养apoE-/-小鼠，HMGCR、SREBP-2和LDLr的变化在其胆固醇代谢紊乱中可能具有重要作用。

　　【关键词】　ApoE-/-小鼠;胰岛素抵抗;胆固醇;基因

　　doi:10.3969/j.issn.1006-6187.2012.04.016

　　Changes of HMGCR, SREBP-2 and LDLr mRNA expression in high-fat induced insulin resistance apoE-/-mice

　　TANG Shi-guo, LI Ling, YANG Gang-yi, et al. Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China

　　Corresponding author:YANG Gang-yi, E-mail：gangyiyang@yahoo.com.cn

　　【Abstract】ObjectiveTo investigate the effects of high-fat induced insulin resistance (IR) on gene-related cholesterol metabolism in apoE-/- mice.MethodsHealthy male apoE-/- mice were randomized into normal diet group (NF group, n=10) and high-fat group (HF group, n=10) and were fed for 16 weeks. The mRNA expressions of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), sterol regulatory element binding protein-2 (SREBP-2), and low density lipoprotein receptor (LDLr) of the hepatic tissues were measured by quantitative real-time PCR.ResultsCompared with the NF group, the fasting blood glucose (FBG), fasting plasma insulin (FIns), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA) were significantly increased (all P<0.01), while the mRNA expression of HMGCR, SREBP-2, and LDLr were significantly decreased in the hepatic tissues of apoE-/- mice (P<0.01 and P<0.05) in the HF group.ConclusionThe down-regulation of HMGCR, SREBP-2 and LDLr might contribute to the disorder of cholesterol metabolism in high-fat fed apoE-/- mice.

　　【Key words】ApoE-/- mice; Insulin resistance; Cholesterol; Genes