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目的 观察胰岛素、胰岛素原对HepG2细胞纤维蛋白溶解酶原激活物抑制物 1(PAI 1)基因表达的影响。方法 将HepG2细胞置于 10 -7mol/L胰岛素培液中 2 4小时使胰岛素受体下调 ,将HepG2细胞诱导成为胰岛素抵抗的HepG2细胞 ,然后分别用胰岛素、胰岛素原 (10 -9mol/L)持续刺激HepG2细胞 2 4小时 ,检测培养液中PAI 1的活性、含量及胞浆中PAI 1mRNA水平。 结果(1)基础状态下胰岛素抵抗和非胰岛素抵抗的HepG2细胞PAI 1活性、含量及mRNA水平差异无显著性。 (2 ) 10 -9mol/L胰岛素或 10 -9mol/L胰岛素原刺激 2 4小时 ,胰岛素抵抗的HepG2 (IR HepG2 )细胞PAI 1活性、含量及mRNA水平明显高于非胰岛素抵抗的HepG2 (NIR HepG2 )细胞。 (3) 10 -9mol/L胰岛素和胰岛素原同时刺激 2 4小时 ,胰岛素抵抗的HepG2细胞PAI 1活性、含量明显高于二者之一单独刺激。 (4) 10 -4 mol/L二甲双胍可明显抑制HepG2细胞PAI 1mRNA的过度表达。 结论胰岛素抵抗状态下免疫反应性胰岛素水平升高 ,胰岛素抵抗的HepG2细胞PAI 1合成对胰岛素刺激的反应性增强是导致PAI 1活性升高的主要原因。 10 -4 mol/L二甲双胍可在mRNA水平抑制PAI 1的合成。
Objective To observe the effects of insulin and proinsulin on the expression of plasminogen activator inhibitor 1 (PAI 1) in HepG2 cells. Methods HepG2 cells were treated with 10 -7 mol / L insulin for 24 hours to downregulate insulin receptor, HepG2 cells were induced into insulin resistant HepG2 cells and then treated with insulin and proinsulin (10 -9 mol / L) respectively HepG2 cells were stimulated for 24 hours. The activity and content of PAI1 in the culture medium and the level of PAI1 mRNA in the cytoplasm were measured. Results (1) PAI 1 activity, content and mRNA level of HepG2 cells in insulin resistance and non-insulin resistance were not significantly different at baseline. (2) The PAI1 activity and mRNA level in HepG2 (IR HepG2) cells stimulated by 10 -9 mol / L insulin or 10 -9 mol / L proinsulin for 24 hours were significantly higher than that of non-insulin resistant HepG2 cells (NIR HepG2 )cell. (3) The PAI1 activity in HepG2 cells stimulated by 10 -9 mol / L insulin and proinsulin for 24 hours was significantly higher than that of HepG2 cells stimulated by either alone. (4) 10 -4 mol / L metformin significantly inhibited PAI 1 mRNA overexpression in HepG2 cells. Conclusions The level of immunoreactive insulin in insulin resistance is increased. The increased reactivity of PAI 1 synthesis in insulin resistant HepG2 cells to insulin stimulation is the main reason leading to the increase of PAI 1 activity. Metformin at 10 -4 mol / L inhibited PAI 1 synthesis at the mRNA level.