胰岛素抵抗对巨噬细胞ACAT-1表达的影响及罗格列酮的干预作用

Effects of ligand-activation of peroxisome proliferator activated receptors-γ (PPAR-γ) on expression of ACAT-1 with high concentrations of insulin and glucose

目的进一步探讨动脉粥样硬化的发生机制及罗格列酮的干预作用。及过氧化物酶体增殖物激活受体-γ(PPAR-γ)高亲和性配体罗格列酮的干预作用。方法体外培养人单核细胞系THP-1细胞,诱导分化为巨噬细胞,分别采用高浓度胰岛素、葡萄糖和不同浓度罗格列酮进行干预,实时定量PCR法检测巨噬细胞人巨噬细胞酰基辅酶A胆固醇酰基转移酶-1(ACAT-1)mRNA表达水平,Western blot检测其蛋白表达。结果在高浓度胰岛素和葡萄糖状态下巨噬细胞ACAT-1m RNA和蛋白表达明显增加(P<0.01);罗格列酮可明显下调其表达且呈浓度依赖性。结论胰岛素抵抗状态下巨噬细胞ACAT-1表达水平升高,罗格列酮可明显下调其表达;此可能为其发挥抗动脉粥样硬化作用的机制之一。

Objective To investigate the effects of ligand-activation of peroxisome proliferator activated receptors-γ （PPAR-γ） on expression of Acyl-CoA： cholesterol acyhransferases-1 （ ACAT-1 ） with high concentrations of insulin and glucose in cultured human macrophages. Methods THP-1 cells were incubated with PMA for 48 hours then exposed to insulin, glucose and rosiglitazone. ACAT-1 expression levels were determined by Real-time Quantitative polymerase chain reaction and Western blot, respectively. Results （ 1 ） high concentrations of insulin and glucose enhanced significantly ACAT-1 mRNA and protein levels. （2）PPAR-γ activated by rosiglitazone significantly inhibited ACAT-1 expression in a concentration-dependent manner. Conclusion PPAR-γ activated by rosiglitazone may result in decrease of ACAT-1 expression levels up-regulated by high concentrations of insulin and glucose, which played an important role in fighting back the human atherogenesis.