RNAi介导的脂联素基因沉默对ApoE基因敲除小鼠糖脂代谢的影响

探讨脂联素基因表达缺陷对ApoE基因敲除(ApoE~(-/-))小鼠糖脂代谢的影响.注射短发卡RNA(shRNA)腺病毒后高脂喂养的ApoE~(-/-)小鼠(ADI组)血浆脂联素水平明显低于普食喂养(NF)、单纯高脂喂养(HF)和空载腺病毒高脂对照组(GF,均P<0.01).3组高脂喂养的APOE~(-/-)小鼠体重、空腹血糖、血浆游离脂肪酸、总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和血浆胰岛素水平明显高于NF组(均P<0.01),而ADI组与HF和GF组相比,游离脂肪酸、总胆同醇、甘油三酯、LDL-C、HDL-C和血浆胰岛素水平增高更为明显(P<0.01或P<0.05),提示长期高脂饲养和脂联素基因表达缺陷使ApoE~(-/-)小鼠具备较为典型的糖脂代谢紊乱和胰岛素抵抗的病理生理表现.

Effects of RNA interference-mediated adiponectin gene silence on glucose-lipid metabolism in ApoE gene knock-out mice

The effect of RNA interference-mediated adiponectin gene silence on glucose-lipid metabolism in apolipoprotein E gene knock-out(ApoE~(-/-)) mice was studied. The plasma adiponectin level in ApoE~(-/-) mice with high-fat diet and adiponectin short hairpin RNA (shRNA) adenovirus injection (ADI group) was significantly lower than that in ApoE~(-/-)mice with high-fat diet(HF group), normal-chow(NF group)and naked adenovirus injection (GF, both P<0.01). Fasting blood glucose, fasting plasma insulin, free fatty acids, total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and body weight were significandy elevated in three high-fat diet groups compared with in NF group, (P<0.01). However, fasting plasma insulin, free fatty acids, total cholesterol, triglycerides, LDL-C, and HDL-C in ADI group were significantly higher than those in HF and GF groups(P<0.01 or P<0. 05). A typical clinical phenotype of glucose-lipid metabolism and insulin resistance in ApoE~(-/-) mice can be induced by high-fat feeding and adiponecting gene silencing.