KCN基因对小鼠脂代谢的影响及其机制初探

发布时间：2019-01-08 09:57

【摘要】：目的研究钾离子电压门控通道(potassium voltage-gated channel,KCN)基因对小鼠脂代谢的影响及其相关信号通路,为治疗糖尿病的脂肪异常提供新的治疗靶点。方法采用KCN基因敲除的小鼠模型及对照C57BL/6野生小鼠动物模型,检测三酰甘油、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇等脂代谢相关指标。HE染色观察小鼠肝脏组织脂肪变。Western blotting法测定小鼠肝脏组织腺苷酸激活蛋白激酶[adenosine 5'-monophosphate(AMP)-activated protein kinase,AMPK]通路相关蛋白的表达。结果 KCN基因敲除小鼠较野生型对照小鼠血清中三酰甘油、总胆固醇和低密度脂蛋白胆固醇浓度均明显增高,差异有统计学意义(P0.05)高密度脂蛋白明显降低,肝脏HE染色显示基因敲除小鼠肝脏内脂滴的数目和体积均与野生型有明显差异,Western blotting结果显示KCN基因敲除小鼠肝脏组织中磷酸化蛋白激酶B(phosphate-protein kinase B,Phos-AKT)、磷酸化乙酰辅酶A羧化酶(phosphate-acetyl CoA carboxylase,Phos-ACC)、phos-AMPK浓度均较正常对照组小鼠表达量降低,phosACCα水平较正常对照组小鼠明显增高差异有统计学意义(P0.05)。结论 KCN基因对小鼠血脂代谢有保护作用,其作用机制与AMPK的脂肪酸氧化有关。
[Abstract]:Objective to study the effect of potassium voltage gated channel (potassium voltage-gated channel,KCN) gene on lipid metabolism and its related signaling pathways in mice, and to provide a new therapeutic target for the treatment of fat abnormalities in diabetes mellitus. Methods the KCN gene knockout mouse model and the control C57BL/6 wild animal model were used to detect triacylglycerol, cholesterol and high density lipoprotein cholesterol. Low density lipoprotein cholesterol and other related indexes of lipid metabolism. Determination of adenosine 5'-monophosphate (AMP)-activated protein kinase, in liver tissue of mice by. Western blotting method with HE staining Expression of transduction pathway related protein (AMPK). Results the serum levels of triglyceride, total cholesterol and low density lipoprotein cholesterol in KCN knockout mice were significantly higher than those in wild type mice, and the difference was statistically significant (P0.05). Liver HE staining showed that the number and volume of lipid droplets in the liver of knockout mice were significantly different from those of wild-type mice. The results of, Western blotting showed that the phosphorylated protein kinase B (phosphate-protein kinase BPhos-AKT) in liver of KCN gene knockout mice was significantly different from that of wild-type mice. The levels of phosphorylated coenzyme A carboxylase (phosphate-acetyl CoA carboxylase,Phos-ACC) and phos-AMPK were significantly lower than those of normal control mice, and the level of phosACC 伪 was significantly higher than that of normal control mice (P0.05). Conclusion KCN gene has protective effect on lipid metabolism in mice, and its mechanism is related to fatty acid oxidation of AMPK.
【作者单位】：首都医科大学附属北京同仁医院内分泌科;糖尿病防治研究北京市重点实验室;
【基金】：国家自然科学基金(81400824,81370946,81300726) 北京市自然科学基金(7131005)~~
【分类号】：R587.1

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