葡萄糖对L02细胞ANGPTL3表达影响机制的研究

发布时间：2018-04-27 07:19

本文选题：血管生成素相关蛋白3 + 肝X受体　；参考：《重庆医科大学》2008年硕士论文

【摘要】： 目的:观察不同葡萄糖浓度对人肝细胞(L02)内胆固醇合成及HMGCR、LXRα和ANGPTL3基因表达的影响;并在各组加入辛伐他汀干预,进一步说明上述影响作用,研究它们对ANGPTL3基因表达影响的机制,及ANGPTL3在代谢综合征发生中的作用。方法:以L02为研究对象,一组在含不同浓度葡萄糖的培养液中培养24小时;另外一组在含10μmol/L辛伐他汀的不同浓度葡萄糖培养液中培养24小时。采用胆固醇酶联试剂盒检测细胞内胆固醇含量,逆转录-聚合酶链反应(RT-PCR)技术检测L02细胞HMGCR、LXRα和ANGPTL3的mRNA水平,用免疫印迹技术检测L02细胞ANGPTL3蛋白质的表达水平。结果:高浓度葡萄糖培养的L02细胞内胆固醇含量明显高于正常葡萄糖浓度培养组(P0.05),且细胞内LXRα、ANGPTL3 mRNA和ANGPTL3蛋白质表达量也明显高于正常组(P0.05),HMGCR在各组的表达差异无统计学意义(P0.05)。在辛伐他汀干预下,LXRα、ANGPTL3 mRNA和ANGPTL3蛋白质表达量均较未加辛伐他汀组下降(P0.05);胆固醇含量也明显低于未加辛伐他汀组(P0.05);HMGCR表达量也明显低于未加辛伐他汀组(P0.05)。在辛伐他汀干预下,不同葡萄糖浓度组的L02细胞内LXRα、ANGPTL3 mRNA和ANGPTL3蛋白表达量及胆固醇含量依然与葡萄糖浓度正相关。结论:葡萄糖能增加L02细胞内胆固醇含量,上调LXRα和ANGPTL3的表达。辛伐他汀能通过减少细胞内胆固醇的合成抑制葡萄糖对LXRα和ANGPTL3的上调作用。高浓度葡萄糖增加ANGPTL3表达的途径可能是通过增加细胞内总胆固醇含量激活LXRα,而LXRα则引起ANGPTL3 mRNA和蛋白质高表达。糖尿病和脂代谢紊乱可能通过LXRα和ANGPTL3联系起来,ANGPTL3表达量与代谢综合征有关。
[Abstract]:Aim: to observe the effects of different glucose concentrations on cholesterol synthesis and the expression of LXR 伪 and ANGPTL3 genes in human hepatocytes, and to investigate the effects of simvastatin on the expression of ANGPTL3 gene. And the role of ANGPTL3 in metabolic syndrome. Methods: L02 was cultured in different concentrations of glucose for 24 hours in one group and in different concentrations of simvastatin in 10 渭 mol/L for 24 hours in the other group. The cholesterol content in L02 cells was detected by enzyme linked assay kit, the mRNA levels of LMGCR-LXR 伪 and ANGPTL3 in L02 cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of ANGPTL3 protein in L02 cells was detected by Western blotting. Results: the cholesterol content in L02 cells cultured with high glucose concentration was significantly higher than that in normal glucose culture group (P 0.05), and the expression of LXR 伪 -ANGPTL3 mRNA and ANGPTL3 protein in L02 cells was significantly higher than that in normal group (P 0.05). Under the intervention of simvastatin, the protein expression of LXR 伪 -ANGPTL3 mRNA and ANGPTL3 were significantly lower than that of untreated simvastatin group (P 0.05), and the cholesterol content was significantly lower than that of untreated simvastatin group (P 0.05) and HMGCR expression was also significantly lower than that of untreated simvastatin group (P 0.05). Under the intervention of simvastatin, the expression of LXR 伪 -ANGPTL3 mRNA and ANGPTL3 protein and cholesterol in L02 cells with different glucose concentrations were still positively correlated with glucose concentration. Conclusion: glucose can increase cholesterol content and up-regulate the expression of LXR 伪 and ANGPTL3 in L02 cells. Simvastatin inhibited the up-regulation of LXR 伪 and ANGPTL3 by reducing the synthesis of intracellular cholesterol. High concentration of glucose may increase the expression of ANGPTL3 through the activation of LXR 伪 by increasing the total cholesterol content in the cells, while LXR 伪 leads to the high expression of ANGPTL3 mRNA and protein. Diabetes mellitus and lipid metabolism disorder may be associated with the expression of ANGPTL3 by LXR 伪 and ANGPTL3.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R341

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