【摘要】 目的研究高糖作用下人肾小球系膜细胞(HMC)中过氧化物酶体增殖物激活受体(PPAR)家族的表达及转录活性的变化,探讨PPAR介导的信号转导途径在糖尿病性肾病发生发展中的作用。方法使用3层滤网法分离HMC,3～7代细胞用于实验。HMC分为正常对照组(5mmol.L-1葡萄糖,NG)、渗透浓度对照组(5mmo.lL-1葡萄糖+25mmol.L-1甘露醇,MG)和高糖组(30mmol.L-1葡萄糖,HG)。mRNA水平及蛋白水平的检测分别采用实时定量PCR和蛋白印迹法。结果NG组HMC中PPARα,PPARγ及PPARδ mRNA均有表达,PPARγ蛋白亦有表达。MG组上述mRNA表达无明显变化。高糖刺激后,PPARα mRNA表达明显高于MG组,PPARγ和PPARδmRNA表达减少,PPARγ蛋白表达亦明显降低,PPARγ激活的基因adipophilin的表达亦减少。结论高糖能上调PPARα基因的表达,抑制PPARγ和PPARδ基因表达,并降低PPARγ的转录活性,提示高糖可能通过PPAR介导的信号转导途径在糖尿病性肾病的发生发展中发挥重要作用。更多还原

【Abstract】 AIM To investigate the function of peroxisome proliferators activated receptors (PPAR) signaling pathway on the occurrence and development of diabetes nephropathy through researching the expressions of PPARα, PPARγ and PPARδ in human glomerular mesangium cells (HMC) after treatment with different concentrations of D-glucose. METHODS The HMC were divided into normal glucose group(5 mmol·L~ -1 D-glucose, NG), osmotic group(5 mmol·L~ -1 D-glucose +25 mmol·L~ -1 mannitol, MG),and high glucose group(30 mmol·L~ -1 D-glucose, HG). The expressions of PPAR and adipophilin mRNA were assessed by using real-time quantitive PCR, and the protein expression of PPARγ was measured with Western blot. RESULTS The PPARα, PPARγ and PPARδ mRNA and PPARγ protein were all expressed in HMC in NG and no obvious changes in these genes were found in MG. The mRNA expression of PPARα was higher in HG group than that in MG group, while the mRNA of PPARγ and PPARδ were depressed in HG group. High glucose also suppressed PPARγ protein and adipophilin gene expressions. CONCLUSION In hyperglycemia, the PPARα gene expression was up-regulated, and the gene expressions of PPARγ and PPARδ were down-regulated. Otherwise the activity of PPARγ was also suppressed. These results demonstrated that PPAR signal transduction pathway may play an important role in the occurrence and progression of diabetes nephropathy.更多还原