醛固酮对3T3-L1脂肪细胞PTEN及p-Akt蛋白表达的影响

目的 观察胰岛素抵抗（IR）的脂肪细胞中Aktser473磷酸化（p-Akt）水平和与张力蛋白同源10号染色体缺失的磷酸酶基因（PTEN）蛋白的表达，以及醛固酮和螺内酯处理后上述蛋白表达的变化，从而探讨醛固酮在IR发病机制中的作用。方法 通过地塞米松与胰岛素共同诱导3T3 L1前脂肪细胞建立IR模型，western blots方法检测正常分化及IR的脂肪细胞PTEN蛋白和p-Akt水平，观察醛固酮和螺内酯对细胞PTEN蛋白表达及p Akt水平的影响。结果 IR脂肪细胞PTEN的蛋白水平较正常分化脂肪细胞显著升高［（0.83±0.11）vs（0.63±0.06）,P＜0.05］,高浓度醛固酮可增加PTEN蛋白表达，经螺内酯处理后PTEN蛋白表达明显下调（P均＜0.05）；IR脂肪细胞模型p-Akt水平明显低于正常分化脂肪细胞［（0.52±0.12）vs（0.78±0.12）,P＜0.05］，高浓度醛固酮可下调p-Akt水平，螺内酯可部分逆转醛固酮的抑制作用（P均＜0.05）。结论 醛固酮可能通过PI3K-AKT通路导致IR的发生。

Effect of aldosterone on PTEN expression and the PI3K-Akt pathway in 3T3-L1 adipocytes

Objective    To investigate the effects of aldosterone  on the expression of phosphoserine 473-Akt and PTEN in normal or insulin resistant adipocytes，  with the aim to explore the role of  aldosterone in the pathogenesis of insulin resistance. Methods    Insulin resistant 3T3-L1 adipocytes were induced by dexamethasone and insulin. The protein expressions of  PTEN and phosphoserine 473-AKT in normal and insulin resistant adipocytes treated with aldosterone or  spironolactone were measured by Western blot. Results    Compared with normal adipocytes, expression of PTEN protein increased（0.83±0.11）vs（0.63±0.06）, P＜0.05］ and phosphoserine 473-AKT protein  decreased（0.52±0.12）vs（0.78±0.12）, P＜0.05］ in insulin resistant models. Aldosterone-induced up regulation of PTEN and degradation of phosphoserine 473 AKT was markedly attenuated by spironolactone,  a mineralocorticoid receptor antagonist（all P＜0.05). Conclusion    Aldosterone induces insulin resistance possibly via the PI3K-Akt pathway in 3T3-L1 adipocytes.